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Biomedical subjects

P Arlock

Publications and source records attributed to P Arlock.

35 records · Page 2Linked to original sources
PubMed1988

Electrophysiological effects of amperozide in papillary muscles from ferrets, guinea-pigs and rabbits.

Amperozide, a novel psychotropic agent, in concentrations lower than 10 microM caused a homogenous prolongation only of the action potential in both guinea-pig and rabbit papillary muscle. In concentrations greater than or equal to 10 microM, amperozide caused a flattening of the action potential plateau and the later part of the repolarization phase became slower (longer), probably reflecting an impaired repolarizing Na-Ca exchange current. The overshoot (OS) and the rate of rise of the action potential (dV/dtmax) were depressed. It is concluded that amperozide has a blocking action on the transmembrane calcium current since Isi (second inward current), DIA (depolarization induced automaticity) and the peak force of contraction were depressed. The blocking of the Isi was use-dependent resembling the actions of calcium-antagonists like verapamil, except that it was less potent at equimolar concentrations. Amperozide in concentrations where it acted as an Isi-blocker (above 10 microM), had depressing effects only on ouabain-induced oscillatory events. No major differences in the effects of amperozide were apparent between guinea-pig, ferret or rabbit papillary muscles.

Action Potentials↗
PubMed1988

Effects of enprofylline, theophylline and terbutaline on second inward currents in papillary muscles from ferrets and guinea-pigs.

In ferret and guinea pig papillary muscles enprofylline (10 microM-10 mM) and theophylline (0.1-2 mM) alone or in combination with terbutaline (0.05 microM-0.1 microM) decreased the action potential duration and increased the plateau height, increased the peak force of contraction and facilitated the depolarization-induced automaticity. In voltage clamp, the xanthines alone or in combination with terbutaline increased second inward currents, ICa,f and ICa,2, but had relatively less effect on the time-dependent outward current. No qualitative differences between enprofylline and theophylline could be detected but the former was about 5 times more potent in increasing ICa,f. In clinically relevant concentrations, enprofylline and theophylline alone, or in combination with terbutaline caused a small (2-5%) shortening of the action potential.

Action Potentials↗
PubMed1985

Intercellular voltage gradient between oocyte and nurse cell in a polychaete.

In the polychaete Ophryotrocha labronica the oocyte is supported during vitellogenesis by a single nurse cell, which is cytoplasmically contiguous with the oocyte through an intercellular bridge. Our electrical measurements demonstrate a marked potential difference (22-32 mV) between the oocyte and the nurse cell in mid-vitellogenesis, suggesting an electrophoretically caused migration of nurse cell constituents into the oocyte. Possibly this potential gradient helps to create a developmental prepattern in the oocyte, a role postulated for similar gradients within the oocyte-nurse cell complex of the Cecropia moth.

Animals↗
PubMed1985

Effects of sodium substitutes on transient inward current and tension in guinea-pig and ferret papillary muscle.

We used ouabain-treated guinea-pig and ferret papillary muscles to study transient inward current (Iti), after-contractions, and tonic tension development during voltage-clamp pulses. Li, sucrose and choline were used isosmotically as Na substitutes to evaluate the effect of altering the Na equilibrium potential. We were unable to detect outward Iti at any potential up to +30 mV in normal or Na-depleted solutions. However, reduction of Na had a biphasic effect on Iti, initially increasing it and then reducing it at all clamp potentials from -50 to +20 mV. After-contractions were also initially increased and, in sufficiently Na-depleted solutions, decreased by reduction of extracellular Na. However, the peak in the after-contraction always occurred later than the increase in Iti and frequently coincided with the maximum suppression of the current. Complete suppression of after-contractions was not often achieved and always required more complete Na replacement than Iti suppression. Tonic tension responses were reduced by Na replacement, usually in synchrony with the reduction of Iti. The responses of Iti to Na replacement are consistent with a model of electrogenic Na-Ca exchange over the potential range positive to -50 mV. The responses deviate from the predictions of the model at more negative potentials. The results are consistent with the previous proposal that oscillatory changes in internal free Ca concentration underlie both Iti and after-contractions.

Action Potentials↗
PubMed1985

Amrinone effects on electromechanical coupling and depolarization-induced automaticity in ventricular muscle of guinea pigs and ferrets.

The effects of the cardiotonic agent, amrinone (0.05-4 mM), on electrical and mechanical activities of ferret and guinea-pig papillary muscles were studied using current and voltage clamp (single sucrose gap) techniques. In current clamp studies, amrinone increased, in a dose-dependent manner, contractile force elicited by action potential in both species. Depolarization-induced automaticity was facilitated in ferret muscles at all maximum diastolic potentials between -70 and -15 mV. Facilitation of automaticity in guinea-pig muscles occurred only at potentials more negative than -35 mV and was suppressed at more positive potentials. Cimetidine (10 microM) partially reversed the effects of amrinone on automaticity in both species. In voltage clamp studies, amrinone increased the slow inward current. Steady-state outward current was increased in guinea-pig but not in ferret muscles. A dual effect of amrinone on tension was observed. Amrinone was found to increase phasic tension of ferret papillary muscles only for depolarizations lasting less than 250 to 300 msec. For longer depolarizations, amrinone decreased the phasic tension (in a dose-dependent manner), whereas the tonic tension was not modified. The decrease as well as the increase in tension was associated with an increase of the slow inward current. The results suggest that amrinone may be arrhythmogenic and may have an intracellular action at the sarcoplasmic reticulum level (partial inhibition) in addition to its action on the calcium current.

Action Potentials↗
PubMed1983

Diltiazem and verapamil preferentially block inactivated cardiac calcium channels.

Diltiazem has been proposed to act by blocking calcium channels of cardiac and smooth muscle since it has pharmacological [12-14] and clinical [10] effects that resemble those of verapamil, an agent that has been shown to block these channels [3]. However, block of the slow inward current by diltiazem has not been directly demonstrated. In fact, it has been suggested that diltiazem has an entirely different mechanism of action [7]. We therefore studied the blocking effects of diltiazem and verapamil on cardiac calcium channels by measuring the slow inward current in voltage-clamped ferret myocardium. Both drugs blocked the slow inward current in a use-dependent fashion, i.e. the block was enhanced by increased frequency of activating clamps and by more positive holding potentials. However, we found that short single activating clamps resulted in minimal block, whereas prolonging the clamp step progressively enhanced the blockade. Thus, a single long clamp caused as much blockade as a train of shorter pulses. These results demonstrate that diltiazem and verapamil block the slow inward current by binding to calcium channels in a state-dependent fashion, i.e. inactivated channels have a high affinity for the drugs, while rested and open channels have a lower affinity.

Animals↗
PubMed1982

Actions of prenalterol, a new cardioselective beta1-agonist, terbutaline and isoprenaline on electrophysiological and mechanical parameters of guinea pig atrial and papillary muscles.

The electrophysiological and mechanical effects of prenalterol on the isolated guinea pig atrial trabeculae and papillary muscles were compared with those of terbutaline and isoprenaline. Isoprenaline was the most potent of the drugs tested on all parameters studied. Prenalterol, on the other hand, failed to induce any changes in the atrial action potentials. The action potential duration was shortened in the atrial trabeculae by terbutaline and isoprenaline. All three substances shortened the action potential in the papillary muscles. In addition, isoprenaline increased the plateau height, and like terbutaline, increased the rate of repolarization during phase 3. Neither prenalterol nor terbutaline changed the effective refractory period in the atrial trabeculae whereas isoprenaline shortened it. All three substances shortened this parameter in the papillary muscles. The developed force and the rate of developed force were increased by all three substances. In addition, the total twitch duration was decreased.

Action Potentials↗
PubMed1981

Actions of lofepramine, a new tricyclic antidepressant, and desipramine on electrophysiological and mechanical parameters of guinea pig atrial and papillary muscles.

The effects of lofepramine on the isolated guinea pig atrial trabeculae were compared with those of desipramine. The preparations were taken from the same animal and mounted in the same tissue bath. All parameters were recorded in parallel. Lofepramine 10 microM was shown to exhibit minor changes in the transmembrane action potential duration only. The action potentials of the atrial trabeculae were prolonged, whereas they were shortened in the papillary muscles. Desipramine was about ten times more potent than lofepramine, but produced similar qualitative changes. Desipramine 10 microM and lofepramine 100 microM showed local anaesthetic properties: a decreased overshoot without a decreased resting potential, a decreased and rate-dependent Vmax, and a decrease in propagation velocity. After the addition of either drug in a lower concentration, a transient increase in force development and a concomitant increase in repolarization phase height (atrial trabeculum) or plateau length (papillary muscle) were recorded. The steady state effect on the force development was a decrease accompanied by a shortening of the action potential duration (papillary muscle). It is suggested that the action of lofepramine 100 microM and desipramine 10 microM on phase 0 of the action potential are produced by blockage of the fast sodium channel. The transient increase in developed force and the increase in repolarization phase height (atrial trabeculum) or plateau length (papillary muscle) could be caused by inhibition of the membrane re-uptake system for released noradrenaline. The steady state shortening and flattening of the plateau (papillary muscle) and the decrease in force development could be the cause of a block in the slow channel system.

Action Potentials↗
PubMed1979

The influence of the surface electrogram on the rising phase of the mammalian cardiac action potential.

1. When guinea pig cardiac tissue is stimulated, the rising phase of the action potential is influenced by the shape of the concomitant local surface electrogram. This, in turn, depends on the direction of the wave of excitation passing the recording microelectrode. 2. A symmetrical biphasic surface electrogram yields sigmoid upstrokes with masimum upstroke velocity (Vmax) lower than when it is either zero or uniphasic and negative. 3. When the main direction of the depolarization wave in guinea pig ventricular myocardium is receding from the recording microelectrode, giving rise to negative uniphasic extracellular potentials, a notch might distort the registration of the rising phase of the action potential. 4. When the main direction of the depolarization wave is approaching the recording microelectrode, giving rise to positive uniphasic extracellular potentials, Vmax is transferred to less negative membrane potentials. 5. The extracellular surface electrogram influences the overshoot of the action potentials of the normal atrial and depressed (D-600) ventricular myocardium and is changed, depending on how the wave of excitation passes the recording microelectrode.

Action Potentials↗
PubMedDate not supplied

Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction by an intracellular calcium-dependent mechanism.

The potentiating effect of neuropeptide Y (NPY) was examined by testing the influence of putative inhibitors of calcium entry on the NPY-enhanced contractile response to noradrenaline in the guinea pig uterine artery. In order to examine the involvement of voltage sensitive calcium entry mechanisms we recorded the effect of noradrenaline and NPY on the membrane potential. NPY (100-300 nM) enhanced noradrenaline-evoked vasoconstriction. The potentiation by NPY was most prominent in low noradrenaline concentrations (30-300 nM) and the pD10 (-log molar concentration of agonist eliciting 10% of maximum contraction) value was increased from 6.43 +/- 0.07 to 6.97 +/- 0.11 (P < 0.001, n = 6). Inhibition of extracellular calcium influx shifted concentration-dependently to the right the concentration-response curve for noradrenaline but potentiation by NPY still remained. The intracellular calcium chelator quin-2 AM selectively abolished the NPY-induced enhancement of the contractile response to noradrenaline. In contrast, quin-2 AM (10-30 microM) had no inhibitory effect on the contractile response to noradrenaline per se. It is suggested that NPY initiates an intracellular calcium-sensitive mechanism which increase alpha-adrenoceptor sensitivity. This results in a significant increase of sarcoplasmic calcium and stronger contractile responses to noradrenaline.

Animals↗