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Procaine alters fast excitatory postsynaptic current decay in amphibian sympathetic ganglia.

1--The effects of procaine (25-200 microM) on the fast excitatory postsynaptic currents (e.p.s.cs) of bullfrog sympathetic ganglion B cells were studied with a two-microelectrode voltage clamp system. 2--Procaine decreased peak e.p.s.c. size with no measurable decrease in quantal content. 3--The peak e.p.s.c.-voltage relationship was linear in control cells, but showed a marked nonlinearity in cells treated with procaine so that peak e.p.s.c. size decreased progressively at hyperpolarized values of membrane potential. The e.p.s.c. reversal potential was not altered in procaine. 4--Although the e.p.s.c. decay time course was well described by a single exponential in control cells, the decay phase often became complex in the presence of procaine. The decay phase consisted of two components in the presence of procaine which became more obvious with increasing concentration and membrane hyperpolarization. 5--In control cells, the e.p.s.c. time constant of decay increased with membrane hyperpolarization. In the presence of procaine, the first time constant of decay, tauf, increased with hyperpolarization up to -40mV, but then decreased with hyperpolarization between -40 and -100mV. 6--We conclude that procaine has two sites of action at postganglionic sympathetic neurones: (1) it reduces the number of activatable receptor-channel complexes and (2) procaine blocks open synaptic channels. Blockade of open channels became more important with hyperpolarization.

Animals↗

The mechanism by which procaine inhibits catecholamine secretion from bovine chromaffin cells.

1. We have investigated the action of procaine on stimulus-secretion coupling in bovine adrenal chromaffin cells. 2. Procaine inhibited the catecholamine secretion evoked by 500 microM carbachol (CCh) with an IC50 of 35 microM and the associated calcium influx (IC50 60 microM). It inhibited the catecholamine secretion evoked by depolarization with high potassium by less than 20% even at the highest concentrations tested (3.2 mM). 3. The secretion evoked by CCh was associated with an increase in sodium influx. This evoked influx was also inhibited by procaine (IC50 80 microM). 4. This selective action of procaine on the CCh-evoked catecholamine secretion was investigated further by patch-clamp techniques. 5. In agreement with the ion flux studies, procaine inhibited the inward current evoked by CCh. Procaine also altered the spectral characteristics of the noise associated with the agonist-induced current by adding an additional high frequency component. The amplitude of this component showed an e-fold increase for a 55 mV membrane hyperpolarization. 6. Data from cell-attached patches showed that increasing concentrations of procaine produced a progressive fall in the mean channel open time and an increase in mean blocked time. This combination led to a decrease in mean burst length. In addition, Popen was reduced by 50 microM procaine. These changes in channel conducting time were sufficient to account for the reduction in inward current. A limited study of the action of procaine on nicotinic channels in outside-out patches gave similar results. 7. The data were considered in relation to various schemes of anaesthetic-channel interactions. The data did not fit the sequential blocking model or the extended channel block model but could be fitted to a modified sequential blocking model in which the rate constant for channel reopening after block was itself subject to modulation by the anaesthetic and the blocked channel could close without passing through the open state.

Animals↗

Low concentrations of procaine and diethylaminoethanol reduce the excitability but not the action potential amplitude of hippocampal pyramidal cells.

To determine whether concentrations of diethylaminoethanol (DEAE) and procaine below those that reduce the amplitude of action potentials might alter the excitability of brain cells, a single microelectrode intracellular recording technique was used to measure firing threshold and action potential amplitude of pyramidal cells in rat hippocampal slices. At low concentrations of both DEAE (less than or equal to 5 mM) and procaine (less than or equal to 0.5 mM), firing threshold was significantly increased (P less than 0.01), whereas action potential spike amplitude was minimally altered. At higher concentrations, both drugs significantly decreased action potential spike amplitude (P less than 0.025) as well as increased firing threshold (P less than 0.001). Diethylaminoethanol tended to increase threshold relatively more than procaine, when drug concentrations that similarly reduced action potential amplitude were compared. All actions of DEAE and procaine were reversible. Inhibition of action potentials by DEAE and procaine was clearly concentration-dependent (P less than or equal to 0.015). Diethylaminoethanol effects on threshold were marginally concentration-dependent (P = 0.08); procaine did not demonstrate clear concentration-dependent effects (P = 0.33) over the concentrations tested in this study. These similar actions of procaine and DEAE on brain cells suggest a mechanism by which intravenous local anesthetics may contribute to the general anesthetic state. Moreover, it appears possible that procaine metabolism and DEAE accumulation may underlie the prolonged effects sometimes seen after intravenous procaine administration.

Action Potentials↗

Appearance of procaine in spinal fluid during segmental epidural analgesia in cows.

The concentration of procaine in the CSF of 10 adult nonpregnant cows was determined after epidural injection of 5% procaine hydrochloride solution. Samples of CSF were removed through a catheter introduced into the subarachnoid space at the lumbosacral intervertebral space and advanced craniad to the same level as the epidural injection site. The position and the location of the catheter and spinal needle were confirmed radiographically. Segmental analgesia was achieved 8 to 20 minutes after completing the procaine hydrochloride injection and extended between spinal cord segments T12 and L3 on one or both sides of the animal. The average duration of analgesia, as determined by response to superficial and deep muscular pinpricks at the L1 dermatome, was 81.3 +/- 22.8 minutes (min-max, 45-127 minutes). The average subarachnoid concentration of procaine 10 minutes after epidural injection was 120.4 +/- 42.9 microgram/ml. The highest average procaine concentration recorded was 160.7 +/- 63.7 microgram/ml at 25.0 +/- 6.7 minutes after injection. Average procaine concentration was 47.8 +/- 13.5 microgram/ml at cessation of analgesia. A similar concentration of procaine was recovered from the subarachnoid space during either unilateral or bilateral analgesia. Procaine was not found in arterial plasma after the epidural administration of procaine hydrochloride. Subarachnoid threshold concentrations of local anesthetic necessary to produce spinal analgesia were reached after repeated epidural injections, but not after a single administration. It is concluded that segmental epidural analgesia is principally due to anesthesia of dura-covered nerve roots within and outside the epidural space and is minimally, if at all, dependent on the production of analgesia of nerves within the subarachnoid space.

Analgesia↗

The role of intracellular pH changes in heat sensitization by procaine.

Although it has been known for many years that procaine sensitizes cells markedly to hyperthermia, the mechanism by which this occurs is not yet understood. The recent finding in our laboratory that procaine caused an intracellular acidification following heating prompted further studies using carboxy-SNARF-1 to measure the intracellular pH of cells during heating. We found that procaine actually causes an intracellular alkalinization during heating and the intracellular pH is lowered immediately after the extracellular procaine is removed. These results suggest that procaine causes acid loading analogous to ammonium chloride (NH4Cl) loading. Sensitization could not be attributed entirely to this acid shock, since a comparable acid shock with NH4Cl loading following heating caused only a slight sensitization compared to procaine. Heated cells acidified with NH4Cl loading recovered rapidly from the low intracellular pH, whereas the cells acidified with procaine loading did not. Cell sorting demonstrated that the cells which were unable to recover from acidification by procaine had significantly lower survival than those that recovered. Thus, in addition to causing an intracellular acidification following heating, procaine alters cellular processes responsible for recovery from an acid shock.

Adaptation, Physiological↗

The Wolff-Parkinson-White syndrome: pharmacologic effects of procaine amide.

The effect of procaine amide, 10 mg. per kilogram via intravenous infusion, was studied in 13 patients with the WPW syndrome. The delta wave was eliminated by procaine amide in 10 and modified in three patients. This effect lasted between 30 minutes and 8 1/2 hours and was unrelated to the total dose administered. Anterograde A-V conduction was assessed by atrial pacing with increasing rates. More rapid atrial pacing rates with 1:1 A-V conduction were observed in patients who maintained rather than lost their delta wave during pacing. Ventriculoatrial conduction was assessed with ventricular pacing at increasing rates; ventricular conduction time was fixed regardless on the pacing rate. Procaine amide significantly prolonged V-A conduction time in six and blocked V-A conduction in one patient. In addition, A-V and V-A refractory periods were measured by the extrastimulus technique. Two types of responses were observed: (1) Type I or (2) line of identity. A-V nodal refractoriness was observed to be within the normal range. Procaine amide converted anterograde line of identity responses to Type I responses in all patients who had their delta waves eliminated. In this patient group, bypass refractoriness was shorter than A-V nodal refractoriness. Procaine amide was not observed to alter significantly normal A-V conduction as assessed by atrial pacing or A-V refractory period measurements. Furthermore, a significant disparity between the effects of procaine amide on anterograde and retrograde bypass refractoriness was observed. Tachycardias could be induced in nine of the 13 patients with a mean rate of 167.2 +/- 7.9 beats per minute; delta waves were abent during all episodes of tachycardia. Procaine amide prevented tachycardia induction in six of the none patients. Procaine amide therefore demonstrates electrophysiologic effects which would be beneficial for prevention or treatment of reciprocating tachycardias in the WPW syndrome. Moreover, procaine amide would be an ideal agent for the prevention of rapid ventricular rates in patients with the WPW syndrome and atrial fibrillation.

Adolescent↗

Analysis of facial displays and verbal report to assess subjective state in the non-invasive detection of limbic system activation by procaine hydrochloride.

The problem of scalp EEG as a measure of cortical or subcortical activity is particularly relevant to complex partial seizures as the abnormal discharging is frequently limbic in origin [14, 30]. Livingston [38] has suggested that administration of intravenous procaine as a limbic activator and cortical suppressor would be of utility in diagnosing limbic involvement in complex partial seizures. While there is considerable evidence derived from experimental animal models that procaine hydrochloride is a limbic system activator that acts preferentially on subcortical epileptic foci at lower doses than on less active epileptic foci or non-epileptic tissue [2, 4], it was necessary to demonstrate that procaine activates the human limbic system. The non-invasive approach taken in the present study was to compare the published effects of direct electrical stimulation of the human limbic system [31] to the behavioural and subjects effects of intravenous procaine administration. The areas in which we obtained the most robust procaine effects (hallucinations, emotions and alimentary sensations) were also Halgren et al.'s [31] most repeatable effects. The correspondence between electrical stimulation effects and procaine administration effects was striking - with verbal report by patients matching exactly in many instances. Furthermore, analysis of facial displays proved useful in providing access to subjects state fluctuations which would otherwise have gone undetected. The data provide strong evidence that procaine hydrochloride can be used as a human limbic system activator. Future research will investigate the clinical and diagnostic significance of differential response to procaine.

Diazepam↗

Procaine excites nociceptors in cultures from dorsal root ganglion of the rat.

Procaine, a classical local anesthetic, produces, at low concentration (2-200 microM), excitation in a distinct population of small sensory neurons isolated from newborn rats (2D) and cultured for 1-5 days. The excitation or inward current (>50 pA) induced by procaine was observed in 59 out of 78 neurons. Nearly all these procaine-sensitive neurons (56 of 59) were also sensitive to capsaicin while 8 procaine-insensitive neurons responded to capsaicin (1 microM). In procaine-sensitive neurons tested for responsiveness to noxious heat, a 10 s temperature ramp from 24 to 48 degrees C induced an inward current of 413 +/- 47 pA (SEM, n = 27) and this current was enhanced, in the presence of procaine, about 3-fold (2.8 +/- 0.4, SEM, n = 27). The responses to procaine were concentration dependent and underwent pronounced tachyphylaxis after repeated applications. The voltage-current relationship exhibited outward rectification and the apparent reversal at 25 +/- 4.2 mV (SEM, n = 9) suggesting that the current is carried by cations including Ca2+. This procaine effect may offer an explanation for toxic consequence of the clinical use of local anesthetics.

Anesthetics, Local↗

Cerebral blood flow during early cardiopulmonary bypass in man. Effect of procaine in cardioplegic solutions.

Cerebral blood flow (CBF), plasma procaine concentrations, and somatosensory evoked potentials (SSEP) were recorded in 2 groups of patients in whom either a high-procaine cardioplegic solution (Bretschneider's n = 29), or a low-procaine cardioplegic solution (St. Thomas', n = 13) was used. In the Bretschneider's group, marked changes in CBF occurred (p less than 0.001). Mean CBF was 27 (range 18 to 51) ml/(100 g X min) between sternotomy and the onset of extracorporeal circulation (ECC). A mean of 6 minutes after the onset of ECC, and before the administration of Bretschneider's cardioplegic solution, CBF increased to 39 ml/(100 g X min). After administration of the cardioplegic solution, CBF decreased significantly within the first 15 minutes, and then gradually increased to a mean of 68 (range 43 to 108) ml/(100 g X min). Cerebral blood flow was 45 ml/(100 g X min) just after ECC was stopped. Marked plasma procaine concentrations, up to 100 mg/l, were reached just after the infusion of Bretschneider's solution. The flow was significantly reduced (p less than 0.015) in patients with plasma procaine greater than or equal to 10 mg/l, when compared to patients with plasma procaine values less than 10 mg/l. In the St. Thomas' cardioplegic solution group the same reduction in CBF did not occur (p less than 0.02). Despite the depressant effect of procaine on CBF in the Bretschneider group, a consistent brain hyperperfusion was observed in all patients during hypothermic ECC if their blood pressure was sufficient to produce hyperemia. In rats (n = 6), during normothermia without extracorporeal circulation, the effect of procaine was much more pronounced. The CBF fell from a mean resting level of 108 ml/(100 g X min) to 68 and 54 ml/(100 g X min) after 15 and 35 minutes, respectively, of continuous infusion of Bretschneider's solution. The flow returned to the resting level about 40 minutes after termination of the infusion.

Adult↗

Determination of procaine in equine plasma and urine by high-performance liquid chromatography.

The variability in plasma and urine equine procaine measurement between three independent laboratories using current methods led to the development of a sensitive, reliable, and reproducible high-performance liquid chromatographic method. Standardbred mares were administered either a penicillin G procaine preparation intramuscularly or procaine hydrochloride subcutaneously, and blood and urine were collected at defined time intervals. By HPLC the detection limits for procaine in plasma and urine were 1 and 10 ng/mL, respectively. In contrast procaine in plasma could not be detected by GC-NPD, while the urinary detection limit was 50 ng/mL. The concentration of fluoride in the collection tubes and repetitive freeze-thawing modified plasma procaine measurement. Urinary pH was a factor in estimation of urine procaine levels with greater recovery and reproducibility of results at pH 5 as compared to pH 7. This HPLC method provides a simple, sensitive, and reliable quantitation of procaine in equine plasma and urine.

Animals↗

Acceptability and compliance with daily injections of procaine penicillin in the outpatient treatment of syphilis-treponemal infection.

BACKGROUND: In the United Kingdom, it is recommended that syphilis should be treated with intramuscular daily procaine penicillin with or without oral probenecid for 8 to 21 days. However, it has been argued that this regimen would be unacceptable to patients in terms of daily attendance and volume of drug administered, resulting in poor compliance. GOAL: To assess the acceptability of and compliance with daily procaine penicillin for 10 to 17 days in patients attending an East London Genito-Urinary Medicine Clinic with a diagnosis of syphilis-treponemal infection. STUDY DESIGN: The notes of 210 consecutive patients attending with syphilis-treponemal infection who had been offered treatment with daily procaine penicillin, with or without oral probenecid for 10 to 17 days, were reviewed retrospectively. RESULTS: Of 210 patients who were offered daily procaine penicillin, 42 (20%) declined and were given oral doxycycline, amoxicillin, or depot penicillin injections. Of 168 patients who accepted daily procaine penicillin, depending on the stage of infection, 90 (54%) had 1.8 g of daily procaine penicillin together with oral probenecid 500 mg every 6 hours for 17 days (high-dose regimen), 57 (34%) had 0.6 g of daily procaine penicillin for 10 to 17 days (low-dose regimen), and 21 (12%) had mixed-dose regimens ranging from 0.5 to 2.4 g. Of the 90 who had high-dose regimen, 76 (84%) complied with treatment compared with 50 (88%) of 57 who had low-dose regimen. All 21 patients who had mixed-dose regimens complied fully. CONCLUSIONS: Daily procaine penicillin is a well-accepted out-patient regimen with excellent compliance (88% overall) and minimal side effects. Because the high-dose regimen has been shown to achieve treponemicidal levels of penicillin in the cerebrospinal fluid, it is recommended for patients with neurosyphilis or those in whom neurosyphilis cannot be excluded. It also could be considered for patients with concomitant human immunodeficiency virus infection in view of the possible progression to neurosyphilis in those treated with depot penicillin.

Female↗

Preparation and immunological properties of procaine-protein conjugates.

Procaine was conjugated to BSA and rat and rabbit Gf using the carbodiimide method and 14C-procaine as a tracer. The composition of the conjugates could be varied depending on the time of incubation and the concentration of procaine in the reaction mixture. Procaine-BSA conjugates were soluble in water or saline. However, procaine conjugates to rat or rabbit Gf were not readily soluble in saline. These conjugates were good for immunization purposes, but it was cumbersome to work with them when clear solutions were needed, as in the immunochemical procedures used in this study. The immunological properties of the conjugates were studied in rats and rabbits. Rats responded with production of IgGa and precipitating antibodies to the procaine group, but IgE antibodies to the immunogen could not be detected. Furthermore, precipitating antibodies towards the procaine group were raised in rabbits. When BSA was the protein carrier, antibodies to the carrier molecule were also detected in both rats and rabbits. The conjugates of procaine to rat or rabbit Gf did not elicit antibody response to the carrier molecular when used in the homologous species. Hapten inhibition studies suggested that, in the rabbit, antibodies were also produced with specificity directed towards the molecular configuration of the hapten-carrier bond.

Albumins↗

Kinetic characterization of the normal and procaine-perturbed reaction cycles of the sarcoplasmic reticulum calcium pump.

We investigated the effect of the local anesthetic procaine on the activity of the calcium pump protein of sarcoplasmic reticulum (SR) vesicles. Procaine slowed down the rate of calcium uptake by SR vesicles without enhancing the vesicles' passive permeability. This slowing of the unidirectional pumping rate was reflected by the inhibition of the maximal rate of the transport-coupled Ca(2+)-ATPase activity. The inhibition was dependent on Mg2+ concentration; at optimal (i.e. low) concentrations of magnesium, half-maximal inhibition occurred with procaine concentrations close to 15-20 mM. Inhibition of ATPase was not mediated by a change in the properties of the bulk lipid phase. Procaine moderately reduced the true affinity of ATPase for ATP, whereas equilibrium binding of calcium to ATPase in the absence of ATP was virtually not modified by procaine. In fast-kinetics studies, we explored the various intermediate steps in the ATPase catalytic cycle, in order to determine which of them were targets for inhibition by procaine. We found that procaine slowed down ATPase dephosphorylation, an effect which is at least partly responsible for the observed inhibition of overall ATPase activity. In contrast, procaine accelerated the calcium-induced transconformation of unphosphorylated ATPase in the absence of ATP, and altered neither the rate of the Ca(2+)-dependent phosphorylation of ATPase, nor the rate of the dissociation of Ca2+ from phosphorylated ATPase towards the SR lumen, a critical step, the rate of which was measured by a novel fast-filtration method. These results are discussed with respect to the possible site(s) of binding of this amphiphile on the ATPase, and in relation to the contribution of individual steps in the catalytic cycle to the rate limitation of unperturbed SR ATPase activity.

Animals↗

Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts.

The effects of lidocaine, procaine, procainamide and quinidine were studied on organ-cultured embryonic chick (2-3 day-old) ventricular cells. Lidocaine (10(-5) - 10(-4)M), in a dose-dependent manner, reduced the rate of pacemaker discharge, the action potential amplitude (APA), the maximum rate of rise (Vmax) of the upstroke of the action potential and the action potential duration at 50% repolarization (APD50). These changes occurred without alterations in the maximum diastolic potential (MDP). Extracellular electrical field stimulation could still evoke action potentials in cells arrested by 10(-4)M lidocaine, but 10(-3)M lidocaine completely abolished electrical activity. Procaine, procainamide and quinidine, at 5 X 10(-5)M to 10(-3)M, depolarized the cells to around -30 mV and reduced APA and Vmax. Procaine and procainamide increased APD50, but quinidine shortened it. All the effects described disappeared completely in about 40 min of superfusion with drug-free Tyrode solution. Isoprenaline (5 X 10(-7)M) and adrenaline (10(-6)M) restored spontaneous firing of preparations arrested by any of the antiarrhythmic agents and repolarized ventricular cells depolarized by procaine, procainamide or quinidine. Propranolol (5 X 10(-7)M) did not affect the depolarization produced by procaine (5 X 10(-4)M), but antagonized its reversal by isoprenaline. In contrast, isoprenaline (10(-6)M) did not produce recovery of automaticity of preparations arrested by verapamil (10(-5)M). Histamine (10(-5)M) or strontium (10 mM) were not able to restore rhythmic activity in cells arrested procaine. Application of long (10-15 s duration) hyperpolarizing currents did not reverse the blocking effect of procaine, procainamide and quinidine. The input resistance increased during the procaine-induced depolarization. It is suggested that the four agents studied block the slow Na+ channels responsible for the upstroke of the action potential in young chick heart cells. A drug-induced decrease in PK may occur in those cells arrested at low levels of membrane potential.

Action Potentials↗

Procaine in cardioplegia: the effect on EDHF-mediated function in porcine coronary arteries.

OBJECTIVES: Hyperkalemia in cardioplegia impairs the endothelium-derived hyperpolarizing factor (EDHF)-mediated function. This study examined the effect of procaine in cardioplegia on the EDHF-mediated response in porcine coronary arteries. METHODS: An isometric force study was performed in a myograph. Two rings taken from the same artery (diameter 200-450 microm) were incubated with Krebs solution (group I) or 20 mM K+ (group II) with/without procaine (1 mM) at 37 degrees C for 1 hour. The EDHF-mediated relaxation was induced by bradykinin (BK, -10 approximately -6.5 log M) after U46619 (-8 log M, in group I) or K+-precontraction (in group II) in the presence of indomethacin (7 microM), NG-nitro-L-arginine (300 microM), and hemoglobin (20 microM). The membrane potential of a single smooth muscle cell was measured by a microelectrode after superfusion with Krebs solution with/without procaine for 1 hour. RESULTS: The EDHF-mediated relaxation was increased by the treatment with procaine with the EC50 shifted leftward (97.3 +/- 0.6% vs. 83.0 +/- 5.1% at -7 log M and 99.4 +/- 0.6% vs. 96.7 +/- 1.6% at -6.5 log M, p < 0.05; EC50: -8.57 +/- 0.24 vs. -7.92 +/- 0.23 log M, p < 0.05). Procaine decreased the BK-induced hyperpolarization from -72.3 +/- 0.7 mV to -68.8 +/- 0.8 mV (-6.5 log M, p < 0.01). The EDHF-mediated relaxation in arteries exposed to 20 mM K+ was not altered by procaine (49.9 +/- 7.4% vs. 55.8 +/- 7.6%, p > 0.05). CONCLUSIONS: In the coronary arteries, procaine has a depolarizing effect but it enhances EDHF-mediated relaxation. Addition of procaine in cardioplegia did not change the EDHF-mediated endothelial function.

Algorithms↗

Analysis of sodium and potassium conductances in the procaine end-plate potential.

1. The effect of procaine on neuromuscular transmission was studied on the sartorius muscle of the frog, Rana pipiens, with intracellular microelectrodes.2. Mean quantal content of the e.p.p. in high Mg Ringer was little affected by procaine.3. The short circuit effect of the e.p.p. on the action potential, which was an indication of change in potassium conductance (Deltag(K)) during the e.p.p., was investigated on the muscle fibre immobilized in hypertonic Ringer. It was found that procaine had little effect on Deltag(K).4. The equilibrium potential of the e.p.p. (E(e.p.p.)) was measured in hypertonic Ringer. E(e.p.p.) was 12 mV in control experiment and was decreased to 3.1 mV in 10(-4) procaine. The ratio Deltag(Na)/Deltag(K) was calculated to be 2.75 in control and 2.11 in 10(-4) procaine.5. E.p.p.s were recorded extracellularly to study changes in the time course of Deltag(Na) in procaine. Procaine reduced the peak magnitude of Deltag(Na); following the peak, Deltag(Na) fell quickly to a lower level, which decayed much more slowly.6. An end-plate model with separate sodium and potassium pathways is proposed to explain the procaine e.p.p. Procaine is assumed to affect the time course of Deltag(Na).7. E.p.p.s simulated from the proposed end-plate model with theoretical Deltag(Na) and Deltag(K) agreed satisfactorily with actual procaine e.p.p.

Animals↗

The effect of procaine on snake twitch muscle fibres.

1. The effect of procaine on the contractile responses of voltage clamped snake twitch muscle fibres has been investigated. Procaine hydrochloride shortened the duration of contractures produced by long depolarizing pulses. It also reduced the amount of inactivating outward current.2. The rate of repriming was greatly slowed by procaine. At -80 mV, for example, the time to half restoration of contractile response was 6 sec in procaine (5 x 10(-3), w/v) as compared to 1.15 sec in tetrodotoxin (TTX), (1 x 10(-7) w/v). At -100 mV, repriming was still much slower in procaine. However, at -150 mV, repriming in procaine was quite rapid, the time to half recovery being about 0.4 sec.3. After prolonged exposure to procaine, subthreshold depolarizing pulses produced a marked diminution in the contractile response to a subsequent supermaximal depolarization. In some fibres complete inactivation could be produced in the presence of procaine without any contractile response having occurred.

Animals↗

Studies of radiocalcium efflux in single barnacle muscle fibres: effects of procaine and external divalent cations.

1. (45)Ca efflux from single barnacle muscle fibres loaded with radio-calcium by microinjection was studied.2. The (45)Ca washout curve consisted of three exponential phases with half-times of 4.8, 12.6 and 111.1 min.3. Removal of external Ca(2+) reduced (45)Ca efflux by 65%. The (45)Ca efflux recovered upon restoring external Ca(2+), the magnitude of the recovery being dependent upon the external Ca(2+) concentration. 10 mM procaine was found to reduce the magnitude of the recovery.4. Removal of external Mg(2+) resulted in a 38% increase in (45)Ca efflux.5. External application of procaine at pH 7.8 caused a dose-dependent inhibition of (45)Ca efflux. The magnitude of the inhibition was reduced in the presence of low external Ca(2+) concentrations. 10 mM procaine at pH 9.3 caused a biphasic effect: inhibition was followed by stimulation.6. Microinjection of 0.5 M procaine caused only inhibition of (45)Ca efflux, whereas microinjection of 1.5 M procaine caused stimulation followed by inhibition. These effects were observed at an external pH of 7.8 and 9.3.7. Injection of 100 mM-EGTA abolished the stimulatory but not the inhibitory effect produced by procaine injection.8. These results are interpreted as indicating that a major fraction of the (45)Ca efflux involves Ca-Ca exchange which is inhibited by the charged form of procaine in a non-competitive manner at the external surface of the muscle fibre. The stimulatory action is attributed to release by procaine of Ca(2+) from internal binding sites.

Acetates↗