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Influence of the hyperpolarization-activated cation current, I(h), on the electrotonic properties of the distal apical dendrites of hippocampal CA1 pyramidal neurones.

The electrical field application technique has revealed that the electrotonic length of the distal apical dendrites of hippocampal CA1 pyramidal neurones is long compared to the rest of the cell. This difference may be due to an asymmetrical distribution of channels responsible for the leak conductance in distal and proximal membrane segments. One such conductance, the hyperpolarization-activated cation current, I(h), is reported to display an increasing density with distance from the soma along the apical dendrite. Such asymmetry of I(h) could be a major cause of the increased electrotonic length of the distal apical dendrite. In the present study we found that blockade of I(h), by bath application of Cs(+) (3 mM) or ZD7288 (20 microM), reduced the electrical field-induced transmembrane polarization (TMP) in the distal apical dendrites. In some neurones the polarization reversed polarity, reflecting a movement of the indifference point (site of zero polarization) from the distal dendrites, across the recording site to a more proximal position. These effects were more pronounced when Cs(+) and ZD7288 were applied locally to the distal apical dendrites. Bath application of another antagonist of leak conductance, Ba(2+) (1 mM), also decreased the average field-induced polarization. This latter effect, however, did not reach statistical significance. These data suggest that I(h) is partly responsible for the distal location of the indifference point, and indicate that an elevated activity of I(h) contributes to the relatively increased electrotonic length of the most distal part of the apical dendrites.

2-Amino-5-phosphonovalerate↗

Regulation of Ca2+-activated nonselective cationic currents in rat pituitary GH3 cells: involvement in L-type Ca2+ current.

Ionic currents were investigated by a patch clamp technique in a clonal strain of pituitary (GH3) cells, using the whole cell configuration with Cs+ internal solution. Depolarizing pulses positive to 0 mV from a holding potential of -50 mV activated the voltage-dependent L-type Ca2+ current (ICa,L) and late outward current. Upon repolarization to the holding potential, a slowly decaying inward tail current was also observed. This inward tail current upon repolarization following a depolarizing pulse was found to be enhanced by Bay K 8644, but blocked by nifedipine or tetrandrine. This current was eliminated by Ba2+ replacement of external Ca2+ as the charge carrier through Ca2+ channels, removal of Ca2+ from the bath solution, or buffering intracellular Ca2+ with EGTA (10 mM). The reversal potential of inward tail current was approximately -25 mV. When intracellular Cl- was changed, the reversal potential of the Ca2+-activated currents was not shifted. Thus, this current is elicited by depolarizing pulses that activate ICa,L and allow Ca2+ influx, and is referred to as Ca2+-activated nonselective cationic current (ICAN). Without including EGTA in the patch pipette, the slowly decaying inward current underlying the long-lasting depolarizing potential after Ca2+ spike was also observed with a hybrid current-voltage protocol. Thus, the present studies clearly indicate that Ca2+-activated nonselective cationic channels are expressed in GH3 cells, and can be elicited by the depolarizing stimuli that lead to the activation of ICa,L.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Neuropeptide FF selectively attenuates the effects of nociceptin on acutely dissociated neurons of the rat dorsal raphe nucleus.

Intracellular Ca2+ concentration ([Ca2+]i) was measured in neurons, acutely dissociated from the rat dorsal raphe nucleus (DRN), with the fluorescent calcium probe Fluo3. Nociceptin (300 nM) had no effect on resting [Ca2+]i but reduced the magnitude of the [Ca2+]i transient triggered by depolarization in 90% of neurons having polygonal or fusiform perikarya. In 94% of neurons with the same morphology 5-HT (30 microM) also reduced the magnitude of the [Ca2+]i transient. The selective 5-HT(1A) receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-ben zamide hydrochloride (p-MPPI) (0.4 microM) strongly attenuated (by 72+/-7%, n=4) this effect. The responses to nociceptin and 5-HT were not affected by BaCl2 (100 microM). The neuropeptide FF analog [D-Tyr1, (N-Me)Phe3]NPFF (1DMe) altered neither the resting [Ca2+]i nor the [Ca2+]i transient triggered by depolarization but dose-dependently decreased the effect of nociceptin (EC50=1.8 nM, maximal reduction: 68+/-5%). 1DMe had no effect on the response to 5-HT. Another neuropeptide FF analog, exhibiting a different pharmacological activity in mice and rats, [D-Tyr1, D-Leu2, D-Phe3]NPFF (1 microM) also reduced the effect of nociceptin by 74+/-11% (n=4). Few neurons (5 out of 42), either with polygonal/fusiform or smaller ovoid cell bodies, responded to the mu-opioid receptor agonist [D-Ala2, (N-Me)Phe4, Gly-ol5]-enkephalin (DAGO) with a decrease in the depolarization-induced [Ca2+]i transient. 1DMe (100 nM) attenuated this response by 69+/-14%. These results suggest that, at the cellular level, neuropeptide FF selectively counteracts the effects of opioid receptor activation.

Aminopyridines↗

Alterations of cross-bridge kinetics in human atrial and ventricular myocardium.

CONDENSED ABSTRACT: We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricular human myocardium. beta-Adrenergic stimulation increased the minimum stiffness frequency by 18 +/- 3% (p < 0.05). Cross-bridge kinetics are temperature-dependent, with a Q10 of at least 2.7. BACKGROUND: Dynamic stiffness measurements have revealed acute and chronic alterations of actomyosin cross-bridge kinetics in cardiac muscles of a variety of different animal species. We studied dynamic stiffness in right atrial and left ventricular preparations of non-failing and failing human hearts and tested the influence of the temperature and beta-adrenergic stimulation on cross-bridge kinetics. METHODS AND RESULTS: Muscle strips were prepared from right atria and left ventricles from human non-failing and failing hearts. After withdrawal of calcium, steady contracture tension was induced by the addition of 1.5 mM barium chloride. Sinusoidal length oscillations of 1% muscle length were applied, with a frequency spectrum of between 0.1 and 60 Hz. Dynamic stiffness was calculated from the length change and the corresponding force response amplitude. The specific minimum stiffness frequency, which indicates the interaction between cross-bridge recruitment and cross-bridge cycling dynamics, was analyzed for each condition: (1) The minimum stiffness frequency was 0.78 +/- 0.04 Hz in left ventricular myocardium and 2.80 +/- 0.31 Hz in right atrial myocardium (p < 0.01) at 27 degrees C. (2) The minimum stiffness frequency was 41% higher in non-failing compared to failing left ventricular human myocardium. (3) Over a wide range of experimental temperatures, the minimum stiffness frequency changed, with a Q10 of at least 2.7. (4) beta-Adrenergic stimulation significantly (p < 0.05) increased the minimum stiffness to 18 +/- 3% higher frequencies and significantly (p < 0.05) lowered contracture tension by 7 +/- 1%. CONCLUSIONS: The contractility of human heart muscle is not only regulated by excitation-contraction coupling but also by modulation of intrinsic properties of the actomyosin system. Acute and chronic alterations of cross-bridge kinetics have been demonstrated, which play a significant role in the physiology and pathophysiology of the human heart.

Actomyosin↗

Delayed rectifier potassium current in undiseased human ventricular myocytes.

OBJECTIVE: The purpose of the study was to investigate the properties of the delayed rectifier potassium current (IK) in myocytes isolated from undiseased human left ventricles. METHODS: The whole-cell configuration of the patch-clamp technique was applied in 28 left ventricular myocytes from 13 hearts at 35 degrees C. RESULTS: An E-4031 sensitive tail current identified the rapid component of IK (IKr) in the myocytes, but there was no evidence for an E-4031 insensitive slow component of IK (IKs). When nifedipine (5 microM) was used to block the inward calcium current (ICa), IKr activation was fast (tau = 31.0 +/- 7.4 ms, at +30 mV, n = 5) and deactivation kinetics were biexponential and relatively slow (tau 1 = 600.0 +/- 53.9 ms and tau 2 = 6792.2 +/- 875.7 ms, at -40 mV, n = 7). Application of CdCl2 (250 microM) to block ICa altered the voltage dependence of the IKr considerably, slowing its activation (tau = 657.1 +/- 109.1 ms, at +30 mV, n = 5) and accelerating its deactivation (tau = 104.0 +/- 18.5 ms, at -40 mV, n = 8). CONCLUSIONS: In undiseased human ventricle at 35 degrees C IKr exists having fast activation and slow deactivation kinetics; however, there was no evidence found for an expressed IKs. IKr probably plays an important role in the frequency dependent modulation of repolarization in undiseased human ventricle, and is a target for many Class III antiarrhythmic drugs.

Action Potentials↗

Hyperpolarisation of rat mesenteric endothelial cells by ATP-sensitive K(+) channel openers.

Membrane potential responses of rat mesenteric endothelial cells were investigated in intact arteries using sharp electrodes. Levcromakalim, an activator of ATP-sensitive K(+) channels (K(ATP)) induced concentration-dependent hyperpolarisation of the endothelial cells, which was reversible by glibenclamide and ciclazindol, inhibitors of K(ATP). Another K(ATP) activator, diazoxide, also hyperpolarised the endothelial cells. Carbachol induced endothelial hyperpolarisation that was inhibited by combinations of apamin and charybdotoxin, but not Ba(2+) and ouabain. Prior stimulation with levcromakalim inhibited carbachol-induced responses, and this inhibitory effect was also sensitive to glibenclamide. 1, 3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl) -2H-benzimidazol-2-one (NS 1619), an activator of large conductance, Ca(2+)-activated K(+) channels (BK(Ca)), induced only small hyperpolarisations of the endothelial cells. Preincubation of tissues with 18 alpha- or 18 beta-glycyrrhetinic acid, inhibitors of gap junction communication, increased the input resistance and depolarised the endothelial cells, and inhibited the hyperpolarising effect of levcromakalim. It is concluded that activation of K(ATP) causes hyperpolarisation of rat mesenteric endothelial cells, probably through gap junctional transfer of smooth muscle hyperpolarisation, and that this may represent an important modulator of endothelial function.

Adenosine Triphosphate↗

Developmental changes in sympathetic contraction of the circular muscle layer in the guinea-pig vas deferens.

Contractile responses of the circular muscle of the isolated vas deferens to electrical stimulation (10-80 Hz) and to noradrenaline significantly decreased with increasing age in 3-week-, 10-week- and 18-month-old guinea pigs, observed by the cannula insertion method. There were no significant differences in the contractile responses induced by alpha,beta-methylene ATP or BaCl2 between 3 and 10 weeks old, but the responses to alpha,beta-methylene ATP or BaCl2 decreased in 18-month-old guinea pigs. The contractile response to electrical stimulation was monophasic in 3-week-old guinea pigs, a small portion of which remained after the treatment with prazosin. Desensitisation of P2X-purinoceptors with alpha,beta-methylene ATP significantly inhibited the contractile responses to stimulation with relatively low frequencies, and the combination of both prazosin and alpha,beta-methylene ATP abolished the stimulation-induced contractions. In 10-week- and 18-month-old guinea pigs electrical stimulation evoked a transient contraction followed by a second contraction at the offset of the stimulation (the after-response). The after-responses were blocked by prazosin. These results show that the dominant component of sympathetic cotransmission is noradrenaline; a purinergic component also exists in the sympathetic contraction in the circular muscle of the vas deferens in young guinea pigs, but is virtually absent in the later stages of development. The sympathetic contractions of the circular muscles significantly decrease with increasing age and this appears to be due to changes in postjunctional, rather than prejunctional, mechanisms.

Adenosine Triphosphate↗

Inhibition of contractions by tricyclic antidepressants and xylamine in rat vas deferens.

The effects of noradrenaline uptake inhibitors on contractions evoked by electric field stimulation, noradrenaline, clonidine. 5-hydroxytryptamine, ATP, high K+, and BaCl2 in the epididymal half of rat isolated vas deferens were examined. Protriptyline, amitriptyline and xylamine concentration-dependently inhibited monophasic contractions induced by low frequency electrical stimulation (0.3 Hz, 1 ms duration, 60 V). Protriptyline and xylamine inhibited in a noncompetitive manner the contractile response induced by noradrenaline (3 x 10(-8)-3 x 10(-5) M) and the inhibitory effect of protriptyline was reversible, while xylamine produced long-lasting inhibition. All three noradrenaline uptake blockers inhibited the clonidine (3 x 10(-6) M) or 5-hydroxytryptamine (10(-5) M)-induced contraction. Protriptyline and amitriptyline at concentrations of 3 x 10(-6)-3 x 10(-5) M reversibly inhibited the ATP (10(-4) M)-induced monophasic contraction. In contrast, xylamine ((1-3) x 10(-5) M) had no effect. Protriptyline and amitriptyline but not xylamine concentration-dependently reduced the high K+ (6 x 10(-2) M)-induced sustained contraction with respective IC50 values of 1.81 x 10(-6) M and 8.6 x 10(-7) M. Protriptyline and amitriptyline at 10(-5) M reversibly inhibited BaCl2 (3 x 10(-3) M)-induced phasic contractions and xylamine (10(-5) M) had no effect. These findings demonstrate that tricyclic antidepressants might exert direct inhibitory action on mechanical contraction pathway, whilst xylamine, a structurally different inhibitor of noradrenaline uptake, may act mainly at alpha-adrenoceptors and other amine receptors on the smooth muscle of the rat vas deferens as a long-lasting nonselective antagonist, and it at least in part blocks sympathetic transmission.

Adenosine Triphosphate↗

Ba2+ selectively inhibits receptor-mediated contraction of the esophageal muscularis mucosae.

The aim of the present study was to examine the effect of Ba2+ on acetylcholine- and KCl-induced contractions of the guinea-pig esophageal muscularis mucosae. When the muscularis mucosae was pretreated with nicardipine (1 microM), Ba2+ (0.1-30 mM) markedly inhibited the acetylcholine (3 microM)-induced tone, and at 10-30 mM the tone returned to its basal level. In contrast, Ba2+ (0.1-30 mM) slightly increased the KCl (60 mM)-induced tone. Moreover, the Ba2+ (30 mM)-increased KCl tone was completely inhibited by treatment with nicardipine (0.3-1 microM). In conclusion, Ba2+ both selectively inhibits receptor-mediated contraction of the muscularis mucosae and itself permeates through voltage-dependent Ca2+ channels.

Acetylcholine↗

Activation of rat locus coeruleus neuron GABA(A) receptors by propofol and its potentiation by pentobarbital or alphaxalone.

The action of propofol on the rat locus coeruleus was examined using intracellular recording from in vitro brain slice preparations. Concentrations of propofol between 3 and 300 microM were tested. At 100 microM, propofol completely inhibited the firing of all neurons tested (n=34); this was associated with a 5.7-mV hyperpolarization (range 0-16 mV, n=33) and a 35.6% reduction in input resistance (range 7.3-66.1%, n=33). The propofol-induced responses were not affected by 2-hydroxysaclofen (50 microM) or BaCl(2) (300 microM), but were completely blocked by bicuculline methiodide (100 microM) or picrotoxin (100 microM), indicating that propofol acts on GABA(A) receptors. As assessed by inhibition of the spontaneous firing rate, propofol was 5.6-fold more potent than GABA (gamma-aminobutyric acid). Potentiation of the propofol effect by other general anesthetics or other drugs was also investigated. When pentobarbital (100 microM) was tested alone on locus coeruleus cells, no change in membrane potential or input resistance was seen and there was only a 20.3+/-7.2% (n=8) inhibition of firing rate; however, in combination with 30 microM propofol, it caused a 6.1-fold greater increase in membrane hyperpolarization and a 9.7-fold greater reduction in input resistance than 30 microM propofol alone. A relatively low concentration of alphaxalone (10 microM), when tested alone, had little effect on the membrane potential or input resistance and only produced a 46.0+/-8.9% (n=8) inhibition of firing rate; however, in combination with 30 microM propofol, it caused a 9.3-fold greater hyperpolarization and an 8.6-fold greater reduction in input resistance compared with 30 microM propofol alone. In contrast, diazepam caused no potentiation of either propofol- or GABA-induced responses. Our data also indicate that locus coeruleus neuron GABA(A) receptors possess distinctive pharmacologic characteristics, such as blocking of the propofol effects by zinc and insensitivity to diazepam and the direct action of pentobarbital. On the basis of these pharmacologic properties, we suggest that locus coeruleus neuron GABA(A) receptors do not contain the gamma subunit.

Anesthetics↗

Mechanically stripped pigmented and non-pigmented epithelium of the shark ciliary body: morphology and transepithelial electrical properties.

Sections of intact ciliary epithelium and mechanically stripped non-pigmented (NPE) and pigmented (PE) cell layers of adult sharks (Squalus acanthias) were mounted in Ussing-type chambers (area 0.1 cm2). Addition of 10(-5) M forskolin to the aqueous side of intact epithelium significantly increased short-circuit current (Isc) within 15 min and a maximum of approx. 30 microA cm-2 was reached after 45-60 min. Transepithelial potential difference (V) increased from -0.8 mV (aqueous side negative as compared with blood/stromal side) to -1.5 mV, whereas resistance (R) was unchanged (50 omega cm2). Forskolin was without effect when applied to the blood side. In stripped PE preparations (R 15 omega cm2), 10(-5) M forskolin applied to the apical side induced a qualitatively similar change of Isc and V compared with the intact tissue. The forskolin-induced effects were fully reversed by 10(-4) M bumetanide and were not dependent on pretreatment of the tissue with 10(-3) M BaCl2. In stripped NPE preparations resistance was usually less than 10 omega cm2 and was not stable. This is consistent with the morphologic observation that although tight junctions were still demonstrable in stripped NPE cells, the apical membranes were damaged. In preparations taken for light and electron microscopy the stripped PE layer revealed intact epithelial cells. In particular, the basal thirds of the stripped PE cells were in very close contact with each other. These attachment zones may have the appearance of tight junctions. Thus the PE cells of the shark ciliary epithelium can be successfully isolated for transepithelial transport studies. The adenylate cyclase system is present in PE cells, and transepithelial transport of chloride may be regulated by intracellular cAMP.

Animals↗

Abscissic acid specific expression of RAB18 involves activation of anion channels in Arabidopsis thaliana suspension cells.

The abscissic acid (ABA) transduction cascade following the plasmalemma perception was analyzed in intact Arabidopsis thaliana suspension cells. In response to impermeant ABA, anion currents were activated and K(+) inward rectifying currents were inhibited. Anion current activation was required for the ABA specific expression of RAB18. By contrast, specific inhibition of K(+) channels by tetraethylammonium or Ba(2+) did not affect RAB18 expression. Thus, outer plasmalemma ABA perception triggered two separated signaling pathways.

Abscisic Acid↗

Coupling of rat somatostatin receptor subtypes to a G-protein gated inwardly rectifying potassium channel (GIRK1).

The five different rat somatostatin receptor subtypes (SSTR1-SSTR5) were coexpressed with a subunit of G-protein gated inwardly rectifying potassium channel (GIRK1) in Xenopus oocytes. SSTR2-SSTR5, but not SSTR1 coupled efficiently to the activation of GIRK currents when stimulated by SST14 or SST28. A comparison of the dose-response curves and of the maximum currents obtained indicates that SSTR2 couples most efficiently to this effector, supporting the notion that SSTR2 is involved in activation of potassium conductances by SST in vivo.

Animals↗

Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features.

BACKGROUND: Eosinophilic esophagitis is an inflammatory condition in which there is dense eosinophilic infiltration of the surface lining of the esophagus. Reports of eosinophilic esophagitis pertain almost exclusively to pediatric populations. However, eosinophilic esophagitis is emerging as a clinical affliction of adults. This report describes the clinical and endoscopic findings of eosinophilic esophagitis in the largest cohort of adult patients reported to date. METHODS: Twenty-nine patients (21 men, 8 women; mean age 35 years) with documented eosinophilic esophagitis (>/=15 eosinophils per high-power field in biopsy specimens) and a significant history of chronic dysphagia for solid food (24 patients) were evaluated clinically and endoscopically during a 3-year period (1999-2002). Fourteen patients (48%) had a history of asthma, environmental allergy, or atopy. In a subset of 15 patients, the diagnostic accuracy of endoscopy was compared with that of barium contrast esophagography. RESULTS: Twenty-seven patients (93%) had abnormal endoscopic findings; 25 (86%) had unique esophageal structural changes, associated with a preserved mucosal surface, that were highly atypical for acid reflux injury. Structural alterations seen in adult patients with eosinophilic esophagitis may occur in combination or as a primary characteristic, e.g., uniform small-caliber esophagus, single or multiple corrugations (rings), proximal esophageal stenosis, or 1 to 2 mm whitish vesicles scattered over the mucosal surface. Barium contrast radiography combined with swallow of a barium-coated marshmallow identified 10 (67%) of the primary features observed endoscopically in 15 patients. However, radiography failed to detect other features noted at endoscopy (e.g., only 3/6 patients with proximal stenosis, 5/9 patients with concentric rings and none of 4 patients with small caliber esophagus). Eight of the 29 patients (20%) had a history of chronic heartburn. Twelve patients had been treated with a proton pump inhibitor and only 3 reported some improvement in the severity of dysphagia. CONCLUSIONS: Relatively young age, a history of chronic dysphagia for solid food, and endoscopic detection of unique structural alterations atypical for GERD in an adult patient should prompt a suspicion of EE and subsequent biopsy confirmation. Acid reflux appears to have a secondary role in eosinophilic esophagitis. In an uncontrolled comparison, endoscopy was superior to barium contrast radiography for the diagnosis of eosinophilic esophagitis. The incidence of eosinophilic esophagitis in adults appears to be increasing.

Adult↗

beta-Adrenoceptor agonist accelerates recovery from inactivation of calcium-dependent action potentials.

The voltage-activated Ca2+ channel in cardiac muscle plasma membranes is regulated by beta-adrenoceptor agonist, presumably by cyclic AMP-dependent phosphorylation of membrane proteins associated with this channel. In chick ventricle, we find that isoproterenol accelerates the recovery from inactivation of the maximum rate of rise (Vmax) of Ca2+-dependent action potentials without changing the steady-state inactivation of Vmax. These results confirm and extend those of others who found that beta-adrenoceptor agonists accelerated the repriming kinetics of bullfrog atrial Ca2+ current (iCa) channels. Patch clamp experiments showed that beta-adrenoceptor agonists change the kinetics of iCa channels so as to increase the probability that an iCa channel is available to open, primarily by reducing the intervals between bursts of channel openings. It is concluded that the altered kinetics of iCa channel repriming caused by beta-adrenoceptor agonist in multicellular preparations is consistent with the action of these drugs in increasing the probability of channel opening and the time spent in the open state.

Action Potentials↗

Color stability of dental composites as a function of shade.

STATEMENT OF PROBLEM: The selection of shade of composites for restorative applications may have a significant effect on color degradation through environmental exposure. PURPOSE: This study characterized the color changes in composites as a function of shade through environmental effects such as ultraviolet light exposure. MATERIAL AND METHODS: Five shades of two composites were subjected to ultraviolet light exposure at 37 degrees C for 24 hours after initial storage for 24 hours in distilled water at 37 degrees C. The lightness and chromaticity values of color were measured both before and after ultraviolet light exposure with a Minolta Chromameter. The total color change as well as changes in the lightness and chromaticity values were measured in the CIE L*a*b* scale and analyzed to monitor color degradation, if any. RESULTS: Color degradation was a significant function of shade and occurred primarily as an increase in yellowness. Color changes increased with the lightness of the shade in both composite systems. CONCLUSION: The lighter shades of composites were likely to be subject to higher color degradation through environmental effects of ultraviolet light exposure.

Analysis of Variance↗

Preferential inhibition by ethanol of phorbol ester-induced smooth muscle contraction of guinea pig gallbladder.

In order to investigate how ethanol inhibits the contractility of gallbladder smooth muscle, the effects of different ethanol concentrations were examined on gallbladder contractile responses to stimulants which act on the smooth muscle by different mechanisms. A low concentration (25 mM) of ethanol significantly inhibited the contractile response to phorbol-12,13-dibutyrate (PDBu), but not that to KCl. It also did not significantly affect contractile response to Ca2+ ionophore A23187 in the presence of verapamil or that to Ba2+ in a medium without Ca2+. On the other hand, a higher concentration (200 mM) of ethanol significantly inhibited the contractile responses to PDBu, KCl, Ca2+ ionophore A23187 and BaCl2. These results together with our recent finding that PDBu-induced contraction of guinea pig gallbladder is completely dependent on activation of the voltage-dependent Ca2+ channel suggest that low concentrations of ethanol selectively inhibit the signal transduction of gallbladder smooth muscle cells in the pathway from activation of protein kinase C to that of the voltage-dependent Ca2+ channel, while high concentrations of ethanol inhibit the intracellular common pathway (probably in the cytoskeletal apparatus).

Animals↗