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PubMed1999

Suppressive effect of genistein on rat bone osteoclasts: apoptosis is induced through Ca2+ signaling.

The effect of genistein on osteoclast-like multinucleated cells (MNCs) from rat femoral tissues was investigated. When rat marrow cells were cultured for 7 d in a medium containing either vehicle, parathyroid hormone (10(-8) M) or prostaglandine E2 (10(-6) M), the formation of tartrate-resistant acid phosphatase (TRACP)-positive MNCs was significantly increased. This increase was markedly weakened by the presence of genistein (10(-6) or 10(-5) M). The bone cells isolated from rat femoral tissues were cultured for 48 h in an alpha-minimal essential medium (5% fetal bovine serum) containing either vehicle or genistein (10(-8) to 10(-5) M). Osteoclasts were estimated by staining for TRACP, a marker enzyme of osteoclasts. The presence of genistein caused a significant decrease in the number of osteoclasts. Such a decrease was also seen in the presence of calcitonin (10(-10) to 10(-8) M), dibutyryl cyclic adenosine 5'-monophosphate (DcAMP; 10(-6) and 10(-5) M), calcium chloride (10(-4) and 10(-3) M) or daidzein (10(-7) to 10(-5) M). The suppressive effect of genistein (10(-5) M) was not further enhanced in the presence of calcitonin (10(-8) M), DcAMP (10(-5) M), or calcium chloride (10(-3) M), and was completely abolished by the presence of dibucaine (10(-6) M) or staurosporine (10(-7) M), both of which are inhibitors of Ca2+-dependent protein kinases. Ca2+ ionophore (A23187; 10(-6) M) induced a remarkable decrease in the number of osteoclasts in the absence or presence of genistein (10(-5) M) or calcium chloride (10(-3) M). The present study demonstrates that genistein has a direct suppressive effect on osteoclasts in vitro, suggesting that the isoflavone may induce apoptosis which is mediated through the pathway of intracellular Ca2+ signaling.

Animals↗
PubMed1990

Stability of milrinone and epinephrine, atropine sulfate, lidocaine hydrochloride, or morphine sulfate injection.

The stability of both drug components of admixtures of milrinone and epinephrine, atropine sulfate, lidocaine hydrochloride, morphine sulfate, calcium chloride, or sodium bicarbonate injections was studied. Duplicate solutions of admixtures of milrinone injection 1 mg/mL and epinephrine injection 1:10,000, atropine sulfate injection 1 mg/mL, lidocaine hydrochloride injection 1%, morphine sulfate injection 8 mg/mL, calcium chloride injection 10%, or sodium bicarbonate injection 7.5% were prepared and stored in glass containers at 22-23 degrees C under fluorescent light. Samples were taken immediately and after 20 minutes for assay by high-performance liquid chromatography (HPLC). Milrinone at initial concentrations of 0.10-0.73 mg/mL showed no degradation in any of the solutions during the study period, nor was any degradation observed for lidocaine, morphine, atropine, or epinephrine. Milrinone 0.10-0.73 mg/mL is compatible with atropine sulfate, lidocaine hydrochloride, epinephrine, calcium chloride, or sodium bicarbonate in glass containers stored for 20 minutes at room temperature. These results support the use of milrinone in combination with these agents immediately after the preparation of admixtures.

Atropine↗
PubMedDate not supplied

In vitro and in vivo characterization of scleral implant of indomethacin: role of plasticizer and cross-linking time.

Film-type scleral implants of indomethacin using sodium alginate and PEG 400 and 600 (3, 5, 8, and 10% w/w w.r.t. sodium alginate) as plasticizers were fabricated by solvent casting. The prepared implants were cross-linked by treatment with calcium chloride 10, 20, and 30% w/v solution, for periods between 1 to 24 hr. Uniformity of thickness, weight, and drug content and surface pH of the implants were evaluated. The influence of plasticizer type/concentration and crosslinking time/concentration of calcium chloride on indomethacin release was studied on a static dissolution setup developed by us. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis-induced (intravitreal injection of bovine serum albumin 50 microg/ml) rabbit eyes. The release of indomethacin from the implants was influenced by the concentration and nature of plasticizers used. Chemical cross-linking with calcium chloride was successful in retarding the drug release. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in the implanted eye when compared with the control eye in the rabbits. The implants survived for 2 weeks in vivo.

Animals↗
PubMed2001

Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma.

Interleukin (IL)-9 is a T helper (Th) 2 cytokine recently implicated as an essential factor in determining susceptibility to asthma. Transgenic mice overexpressing IL-9 exhibit many features that are characteristic of human asthma. To better understand the mechanism by which IL-9 mediates the various biologic activities in asthma, we performed suppressive subtraction hybridization with whole lung from IL-9 transgenic and control mice. Here we report the identification of mCLCA3, a calcium-activated chloride channel that was specifically induced in the lung epithelium of IL-9 transgenic mice. Expression of mCLCA3 could also be induced by intratracheal administration of IL-9 or other Th2 cytokines (IL-4, IL-13), but not by interferon-gamma. Moreover, expression of mCLCA3 was induced in the lung of antigen-exposed mice, and this induction could be suppressed by neutralizing IL-9 antibody treatment, indicating IL-9 is both necessary and sufficient to induce mCLCA3 in this experimental model of asthma. Finally, we demonstrate that hCLCA1 is the human counterpart to mCLCA3 and is also induced in vitro in human primary lung cells by Th2 cytokine treatment. Together, these data strongly implicate the involvement of mCLCA3 (in mice) and hCLCA1 (in humans) in the pathogenesis of Th2 cytokine-mediated asthmatic disorders.

Amino Acid Sequence↗
PubMed2006

[Comparative study of the antiarrhythmic activity of magnesium aspartate L-, D- and DL-aspartate stereoisomers].

It seems an established fact that magnesium (Mg) aspartate is effective in prophylaxis and adjuvant therapy of cardiac arrhythmia (e.g. prevention of toxic symptoms during therapy with digoxin). There are claims that L-aspartate salts are better delivery forms for cations such as Mg than D-aspartate salts, and Mg L-aspartate can be more beneficial in the treatment of several forms of primary Mg deficiency than Mg DL- and D-aspartate. Therefore, the purposes of the present work were to compare of antiarrhythmic action of Mg L-, D- and DL-aspartate stereoisomers using CaCl(2)- and aconitine-induced arrhythmia models in rats. It was found that intravenously administered Mg L-aspartate exhibited higher activity compared to Mg D- and DL-aspartate in calcium chloride and aconitine-induced arrhythmias. In rats with arrhythmias induced by calcium chloride Mg L-aspartate compared with Mg D-aspartate and Mg DL-aspartate produced greater decrease of incidence of arrhythmias, increase of time first arrhythmia onset, decrease of percentage of rats that died and increase of duration of life after onset of first arrhythmia. In rats with aconitine-induced arrhythmia Mg L-aspartate surpassed Mg D-aspartate and Mg DL-aspartate in parameters of acute toxicity (LD(50)), effective dose (ED(50)) and antiarrhythmic (therapeutic) ratio (LD(50)/ED(50)).

Aconitum↗
PubMed1991

Role of calcium in the analgesic action of tetrahydroisoxazolepyridinol and muscimol.

The role of calcium in the analgesic activity of 4,5,6,7-tetrahydroisoxazole-(5,4-c) pyridin-2-ol (THIP) and muscimol has been investigated using the acetic acid assay procedure. THIP and muscimol produced significant analgesic response. Whilst neither calcium chloride nor nifedipine in the doses employed significantly altered the number of writhings, calcium chloride antagonized the analgesic responses of THIP and muscimol while nifedipine potentiated them. Similar responses were recorded for morphine. These findings suggest that THIP and muscimol, like morphine, might alter the calcium movements across the plasma membrane to elicit the analgesic response.

Analgesics↗
PubMed1985

Importance of the ileum in neurotensin released by fat.

Neurotensin is a potent stimulant of pancreatic exocrine secretion. Ileal mucosa is the storage site for about 90% of total neurotensin. Release occurs rapidly after a fatty meal and during perfusion of the duodenum and jejunum with fat but not during perfusion of the ileum with fat. To determine the origin of neurotensin released after fat stimulation, we studied the pattern of release of neurotensin before and after resection of the distal two thirds of the small bowel. Six dogs with gastric and duodenal fistulas were studied on different days. All dogs received infusions (in random order) of intraduodenal corn oil (Lipomul) (3 ml/kg/hr) and intravenous calcium chloride (0.36 mmol/kg intravenous bolus, followed by 0.36 mmol/kg/hr infusion) before and 6 weeks after resection of the distal two thirds of the small bowel with preservation of the ileocecal valve. Plasma levels of neurotensin were measured by specific radioimmunoassay. We found that release of neurotensin, in response to both intraduodenal Lipomul and intravenous calcium chloride stimulation, was abolished by resection of the distal small bowel. Before surgery, Lipomul-stimulated release of neurotensin rose to a peak concentration of 51 +/- 17 pg/ml at 30 minutes. After surgery there was no release (the levels were unchanged from basal). Before surgery, intravenous calcium chloride produced a peak release of neurotensin (52 +/- 15 pg/ml) 2 minutes after bolus injection. After surgery, neurotensin was not released by intravenous calcium. We conclude that the source of neurotensin released by perfusion of the proximal gut and by intravenous calcium infusion is the ileum. The release of neurotensin from the distal gut appears to be dependent on a signal from proximal to distal gut. The identity of the signal is unknown but is either a nerve reflex or a peptide agent.

Animals↗
PubMed2004

An improved method of microencapsulation and its evaluation to protect Lactobacillus spp. in simulated gastric conditions.

An improved method of microencapsulation was developed to increase the efficacy of capsules in protecting the encapsulated bacteria under simulated gastric conditions. Lactobacillus acidophilus CSCC 2400 was encapsulated in calcium alginate and tested for its survival in simulated gastric conditions. The effects of different capsule sizes (200, 450, 1000 microm), different sodium alginate concentrations (0.75%, 1%, 1.5%, 1.8% and 2% w/v) and different concentrations of calcium chloride (0.1, 0.2, 1.0 M) on the viability of encapsulated bacteria were investigated. The viability of the cells in the microcapsules increased with an increase in alginate capsule size and gel concentration. There was no significant difference (p>0.05) in the viability of encapsulated cells when the concentration of calcium chloride was increased. Increase in cell load during encapsulation increased the number of bacterial survivors at the end of 3-h incubation in simulated gastric conditions. Hardening the capsule in calcium chloride solution for a longer time (8 h) had no impact on increasing the viability of encapsulated bacteria in a simulated gastric environment. The release of encapsulated cells at different phosphate buffer concentrations was also studied. When encapsulated L. acidophilus CSCC 2400 and L. acidophilus CSCC 2409 were subjected to low pH (pH 2) and high bile concentration (1.0% bile) under optimal encapsulation conditions (1.8% (w/v) alginate, 10(9) CFU/ml, 30 min hardening in 0.1 M CaCl(2) and capsule size 450 microm), there was a significant increase (p<0.05) in viable cell counts, compared to the free cells under similar conditions. Thus the encapsulation method described in this study may be effectively used to protect the lactobacillus from adverse gastric conditions.

Alginates↗
PubMed2002

[Efficacy of treating denture-induced stomatitis by electrically activated aqueous solutions].

The authors investigated the oral mucosa in 35 patients, who were divided into four groups: Group 1 (n = 17) received traditional treatment, Group 1 (n = 18) had the similar treatment supplemented by electrically activated aqueous calcium chloride solutions. The findings have shown that the use of electrically activated aqueous calcium chloride solutions in the complex treatment of orthopaedic stomatitis exert more marked clinical and immunological effects than the traditional treatment (p < 0.001-0.01).

Aged↗
PubMed1990

Calcium-dependent chloride current in neurones of the rabbit pelvic parasympathetic ganglia.

1. Voltage-clamp recordings were made from neurones in rabbit vesical pelvic ganglia by using single microelectrodes filled with 2 M-caesium chloride. Neurones were superfused with Krebs solution containing 300 nM-tetrodotoxin and 50 mM-tetraethylammonium. 2. Depolarizing voltage jumps activated inward currents followed by slowly decaying inward tail currents at -30 to +30 mV, which were accompanied by a large increase in membrane conductance. Both the inward current and tail current were blocked by cobalt (2 mM) or in a Krebs solution containing zero calcium and 12 mM-magnesium. 3. Substitution of barium for calcium enhanced the inward current, while it strongly reduced the tail current. Strontium substitution still exhibited both the inward current and the tail current. 4. Lowering external chloride activity increased the tail current amplitudes without affecting an initial calcium current. The reversal potentials of the tail current, measured using a twin-pulse protocol, were -18 +/- 5 mV (mean +/- S.E.M., n = 8) and +5 +/- 3 mV (n = 5) in Krebs solution and low-chloride (62 mM) solution, respectively, suggesting a calcium-dependent chloride current. 5. Stilbene derivatives, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS, 0.01-1 mM) and 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS, 0.01-1 mM), reversibly and concentration dependently depressed the tail current without affecting the calcium current. 6. Transient (T) and sustained (N and L) types of calcium current were likely to co-exist in neurones of the rabbit pelvic ganglia. Calcium-dependent chloride current was activated by N- and L-type calcium currents but not by T-type current. 7. Activation of the tail current at 0 to +20 mV was described by a single-exponential function. The tail current decayed exponentially at a holding membrane potential of -70 mV. Tail decay time constants were dependent on voltage and duration of the step command. 8. Substantial activation of the calcium-dependent chloride conductance could occur during a post-tetanic after-potential when pelvic ganglia neurones fired action potentials repetitively.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2006

Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family members.

Complex airway diseases such as asthma and chronic obstructive pulmonary disease exhibit stereotyped traits (especially airway hyperreactivity and mucous cell metaplasia) that are variably expressed in each patient. Here, we used a mouse model for virus-induced long-term expression of these traits to determine whether individual traits can be genetically segregated and thereby linked to separate determinants. We showed that an F2 intercross population derived from susceptible and nonsusceptible mouse strains can manifest individual phenotypic extremes that exhibit one or the other disease trait. Functional genomic analysis of these extremes further indicated that a member of the calcium-activated chloride channel (CLCA) gene family designated mClca3 was inducible with mucous cell metaplasia but not airway hyperreactivity. In confirmation of this finding, we found that mClca3 gene transfer to mouse airway epithelium was sufficient to induce mucous cell metaplasia but not airway hyperreactivity. However, newly developed mClca3(-/-) mice exhibited the same degree of mucous cell metaplasia and airway hyperreactivity as wild-type mice. Bioinformatic analysis of the Clca locus led to the identification of mClca5, and gene transfer indicated that mClca5 also selectively drives mucous cell metaplasia. Thus, in addition to the capacity of CLCA family members to exhibit diverse functional activities, there is also preserved function so that more than one family member mediates mucous cell metaplasia. Nonetheless, Clca expression appears to be a selective determinant of mucous cell metaplasia so that shared homologies between CLCA family members may still represent a useful target for focused therapeutic intervention in hypersecretory airway disease.

Animals↗
PubMed2003

Airway surface liquid calcium modulates chloride permeability in the cystic fibrosis airway.

Patients with cystic fibrosis (CF) demonstrate a characteristic defect in epithelial chloride movement, which can be demonstrated in vivo by the nasal potential difference technique. After amiloride pretreatment, the CF airway exhibits only a transient response to perfusion with low-chloride solution, contrasting with the sustained hyperpolarization seen in control subjects. This study further investigated the response to low-chloride solution in the CF airway, examining the interaction between surface divalent ions and the low-chloride response. Sequential perfusion with amiloride, low chloride, and isoproterenol was tested in groups of subjects with CF, with the diluent containing different concentrations of calcium and magnesium, on different days. When the low-chloride response was measured with the nominally calcium-free diluents, the subjects with CF had mean (SEM) responses of 8.0 (0.7), 8.6 (2.4), and 9.6 (1.6) mV in the presence of 0, 1, and 3 mM Mg2+, respectively, significantly different from the response in the presence of divalent ions. However, the subsequent response to isoproterenol was not different in the presence or absence of divalent ions. We hypothesize that perfusion of the CF airway with nominally calcium-free solutions reduces tonic inhibition of chloride secretion.

Adolescent↗
PubMedDate not supplied

Interaction between cholesterol and calcium ions in solution.

Dialysis rates of cholesterol, calcium chloride dihydrate and of their mixture in 90% aqueous dioxane through Visking cellulose membrane were characterized by half-escape times (t1/2) of 2.2, 1.0 and 10.5 hours, respectively. Slow dialysis rate observed with the mixture was due to complex formation between four molecules of cholesterol and two molecules of calcium chloride dihydrate, molecular weight 1800 to 2000. The association constant for this complex in 90% aqueous dioxane was estimated to be 3.9 X 10(14). Rates of dialysis obtained with a natural protein membrane were in the reverse order to those obtained with cellulose membrane. Half-escape times for cholesterol, calcium chloride dihydrate and for their mixture were 0.6, 6.7 and 1.4 hours, respectively. Determinations of milliosmolality of the three solutions by freezing point depression indicated that in the mixture there were fewer osmotically active particles than in their separate solutions of the same molarity, also suggesting formation of the complex which was detected by dialysis experiments.

Calcium↗
PubMed1986

Relationships between calcium and chloride transport in frog skin glands.

Frog skin gland, a furosemide-sensitive Cl(-)-secreting epithelium, exhibits Cl(-)-dependent Ca2+ secretion in response to stimulation by beta-adrenergic agonists. In this study, we further explored the relationships between Cl- and Ca2+ secretion in frog skin using 45Ca fluxes and short-circulating technique. On addition of isoproterenol (ISO) or 8-(p-chlorophenylthio)-cAMP, a significant positive correlation was demonstrated between Ca2+ secretion and Cl- secretion. Because Cl- transport in other Cl(-)-transporting epithelia may be modulated by prostaglandins or by changes in cytosolic Ca2+ activity, in addition to modulation by cAMP, we also examined the effects of prostaglandins (PG)E2 and F2 alpha, indomethacin (INDO), and the calcium ionophore A23187. Treatment with PGE2, PGF2 alpha, or A23187 at a dose of 10(-5) M resulted in marked stimulation in the amiloride-resistant short-circuit current, a reflection of Cl- secretion. This current was inhibited by furosemide addition or removal of Cl- from the bathing medium. However, and in contrast to stimulation with ISO or cAMP, PGE2, PGF2 alpha, and A23187 failed to induce Ca2+ secretion. In addition, the stimulation of Cl- secretion by A23187 was abolished by INDO (10(-6) M) pretreatment. Thus frog skin glands secrete Cl- via two mechanisms: one mediated by beta-adrenergic-cAMP stimulation and the other by activation of prostaglandin metabolism induced by changes in cytosolic Ca2+. Only the former pathway is associated with Ca2+ secretion. Furthermore, to account for the Cl- dependence of Ca2+ secretion, we postulate the existence of a Ca2+-Cl- cotransport system stimulated by cAMP.

Animals↗
PubMed1994

Calcium-dependent chloride channels in endosomes from rabbit kidney cortex.

Ion channels in endosomal membranes from rabbit kidney cortex were studied after reconstitution into planar lipid bilayers. The most frequently observed ion channel was anion selective (PCl/PK = 13) and had a single-channel conductance of 116 pS when the cis and trans solutions contained 410 and 150 mM KCl, respectively, and a conductance of 90 pS in symmetrical 150 mM KCl solutions. The anion selectivity sequence of the channel was NO3- > F- > Br- > Cl- >> I-. The activity of the channel was voltage dependent such that hyperpolarization of the cis, or cytoplasmic, surface of the channel increased the open probability (Po). The activity of the channel was also highly dependent on the calcium activity of the cis but not the trans solution. Channels were fully active (Po > 0.7) at Ca2+ concentration > 1 microM, but channel activity was completely absent (Po < 0.001) at Ca2+ concentration < 250 nM. The effects of calcium on Po were not voltage dependent. The Cl(-)-channel blocker 2-[(2-cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H-inden -5- yl)oxy]-acetic acid (IAA-94/95) produced a concentration-dependent reversible flickering block of the endosomal channel with a Ki of 15 microM. 4,4'-Dinitrostilbene-2,2'-disulfonic acid, a disulfonic stilbene, also produced a flickering block of the channel with a Ki of approximately 5 microM. Because endosomal Cl- channels are believed to facilitate endosomal acidification, we tested the effects of IAA-94/95 and deletion of Ca2+ on the rate of acidification of intact endosomes. Because neither maneuver affected acidification, we conclude that the 116-pS channel does not participate in endosomal acidification. This channel may be involved in other endosomal processes, e.g., cell volume regulation and control of membrane trafficking.

Acids↗
PubMed2004

Regulation of amniotic fluid volume: intramembranous solute and volume fluxes in late gestation fetal sheep.

OBJECTIVE: Recent studies suggest that amniotic fluid volume is regulated by the rate of intramembranous absorption of amniotic fluid into fetal blood. The purpose of the present study was to determine the simultaneous intramembranous solute and water fluxes to gain insight into the intramembranous transport and amniotic fluid volume regulatory mechanisms. STUDY DESIGN: All major amniotic inflows and outflows, except intramembranous flow, were eliminated in 10 fetal sheep over 8 hours by occlusion of the fetal trachea and esophagus; the fetal urine was drained to the exterior. Amniotic fluid composition and volume were measured before and at the end of the 8 hours. Solute and volume fluxes through the intramembranous pathway were calculated from amniotic fluid concentration and volume changes. Statistical analyses included t-tests, linear regression, and analyses of variance. RESULTS: Amniotic fluid volume decreased by 128 +/- 24 (SE) mL over 8 hours (P < .001), which was correlated only marginally with the fetal to amniotic fluid osmotic gradient (r=0.59; P = .072). Amniotic fluid sodium, chloride, calcium, and bicarbonate concentrations increased (P < .0001), even though there were net outward fluxes of these solutes; these outward fluxes occurred against concentration gradients; and the clearances of these solutes were the same despite widely differing amniotic fluid concentrations and fetal blood to amniotic fluid concentration gradients. With the use of multivariate regression, intramembranous solute fluxes separated into 2 components, which were a primary outward flux that correlated with the volume flux and a minor inward component that correlated with the fetal plasma to amniotic fluid concentration gradient for sodium, chloride, calcium (P < .001), and bicarbonate (P < .02). The concentration-dependent fluxes averaged approximately one third of the bulk fluxes and were in the opposite direction. CONCLUSION: The poor correlation of amniotic fluid volume reduction with the fetal-to-amniotic fluid osmotic gradient shows that the primary mechanism that mediates intramembranous volume flow is not passive osmosis in the normal fetus under basal conditions. The strong correlations of solute fluxes simultaneously with volume flux and concentration gradients suggest that intramembranous solute fluxes are mediated by both bulk flow and passive diffusion. The small size of the passive component relative to the size of the bulk component suggests that intramembranous solute transfer is mediated primarily by bulk flow with a smaller and usually oppositely directed contribution by diffusion down concentration gradients. Bulk flow by vesicular transport is the only known physiologic transport mechanism that is compatible with these data, but it is not known whether this occurs in the amnion or intramembranous blood vessels or both.

Amniotic Fluid↗
PubMed1983

Fluoroacetamide poisoning in man: the role of ionized calcium.

Two cases are reported of severe acute fluoroacetamide poisoning in man, with successful treatment of the life-threatening cardiac arrhythmias by the administration of calcium chloride. The arrhythmias were preceded by prolongation of the QT interval in the ECG. Calcium chloride therapy restored to normal the markedly prolonged QT interval.

Adolescent↗
PubMed1977

Pancreatic acinar cells: localization of acetylcholine receptors and the importance of chloride and calcium for acetylcholine-evoked depolarization.

1. Intracellular micro-electrode recordings of acinar cell membrane potential and resistance were made from the mouse pancreas superfused in vitro. The acinar cells under investigation were stimulated by micro-iontophoretic ACh application from an extracellular AChCl-filled micro-electrode.2. Passing short-lasting ejecting current pulses through the AChCl-electrode caused acinar cell depolarization when the electrode was in an extracellular position not far (< 50 mum) from an acinus impaled by a KCl micro-electrode. After insertion of the AChCl electrode into a neighbouring acinar cell, electrically coupled to the acinar cell already impaled by the KCl-electrode, ejecting ACh current pulses only affected the membrane potential in a direct electrical manner whereas there was no sign of an effect of ACh on the membrane potential.3. Replacing extracellular chloride by sulphate caused a marked increase in the amplitude of the ACh-evoked depolarization. If the membrane potential was recorded with a KCl electrode ACh continued to evoke very large depolarizations even after more than 1 hr exposure to Cl-free solution. If the membrane potential was recorded with a K-citrate electrode the effect of Cl-removal was only transient. Removal of Na(+) during exposure to Cl-free solution reduced the amplitude of the ACh-evoked depolarization somewhat. Readmission of Cl after more than 1 hr of Cl deprivation caused an immediate reversal of the ACh effect into a hyperpolarization.4. Removal of extracellular Ca(2+) caused a marked reduction in the amplitude of small depolarizations evoked by just suprathreshold doses of ACh, whereas there was very little effect on larger depolarizations evoked by maximal or supramaximal ACh ejections. The effect of Ca removal was fully reversible. Addition of Mn after Ca-deprivation was as efficient as Ca in restoring normal electrophysiological responses to small doses of ACh.5. The acinar cell membrane seems only to be responsive to ACh added to the extracellular side and ACh probably causes an increase in membrane Cl permeability in addition to the previously described effects on Na and K permeability. Ca may be important in determining ACh receptor sensitivity.

Acetylcholine↗