Abstract
Biochemical and electrophysiological studies have shown that ethanol potently inhibits voltage-dependent calcium channels in presynaptic nerve terminals in brain. The ability of ethanol to inhibit calcium channels appears to vary from one brain region to another. Chronic ethanol administration results in adaptation of the calcium channels in certain brain regions such that they become tolerant to the inhibitory actions of ethanol. Other sedative-hypnotic drugs, such as barbiturates and benzodiazepines, also inhibit calcium channels but may differ from ethanol in their brain regional potency. These studies suggest that the pharmacological actions of ethanol and other sedative-hypnotic drugs may be linked with alterations in calcium channel function.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Harris RA, Hitzemann RJ: Membrane fluidity and alcohol actions, in Galanter M (ed): Currents in Alcoholism (vol 8). New York, Grune & Stratton, 1981, pp 379–404.
Goldstein DB: Speculations on membrane lipid adaptation as a mechanism for drug tolerance and dependence. Prog Clin Biol Res 27:151–166, 1979.
Sun GY, Sun AY: Ethanol and membrane lipids. Alcoholism Clin Exp Res 9:164–180, 1985.
Kaufman RD: Biophysical mechanisms of anesthetic action. Anesthesiology 46:49–62, 1977.
Harris RA, Schroeder F: Effects of ethanol and related drugs on the physical and functional properties of brain membranes, in Galanter M (ed): Currents in Alcoholism (vol 8). New York, Grune & Stratton, 1981, pp 461–468.
Chin JH, Goldstein DB: Effects of low concentrations of ethanol on the fluidity of spin-labeled erythrocyte and brain membranes. Mol Pharmacol 13:435–41, 1977.
Harris RA, Schroeder F: Ethanol and the physical properties of brain membranes: Fluorescence studies. Mol Pharmacol 20:128–137, 1981.
Lyon RC, McComb JA, Schreurs J, et al: A relationship between alcohol intoxication and the disordering of brain membranes by a series of short-chain alcohols. J Pharmacol Exp Ther 218:669–675, 1981.
Chin JH, Goldstein DB: Drug tolerance in biomembranes: A spin label study of the effects of ethanol. Science 196:684–685, 1977.
Johnson DA, Lee NM, Cooke R, et al: Adaptation to ethanol-induced fluidization of brain lipid bilayers: Cross-tolerance and reversibility. Mol Pharmacol 17:52–55, 1980.
Downes H, Perry RS, Ostlund RE, et al: A study of the excitatory effects of barbiturates. J Pharmacol Exp Ther 175:692–699, 1970.
Downes H, Franz DN: Effects of convulsant barbiturate on dorsal root ganglion cells and dorsal root discharges. J Pharmacol Exp Ther 179:660–670, 1971.
Richter JA, Holtman JR: Barbiturates: Their in vivo effects and potential biochemical mechanisms. Prog Neurobiol 18:275–319, 1982.
Barker JL, Huang L-YM, MacDonald JF, et al: Barbiturate pharmacology of cultured mammalian neurons, in Fink BR (ed): Molecular Mechanisms of Anesthesia (vol 2). New York, Raven Press, 1980, pp 79–93.
Ticku MK, Rastogi SK, Thyagarajan R: Separate site(s) of action of optical isomers of 1-methyl-5-phenyl-5-propylbarbituric acid with opposite pharmacological activities at the GABA receptor complex. Eur J Pharmacol 112:1–9, 1985.
Skerritt JH, MacDonald RL: Multiple actions of convulsant barbiturates on mouse neurons in cell culture. J Pharmacol Exp Ther 230:82–88, 1984.
Krespan B, Springfield SA, Haas H, et al: Electrophysiological studies on benzodiazepine antagonists. Brain Res 295:265–274, 1984.
Schlosser W, Franco S: Reduction of 7-aminobutyric acid (GABA)-mediated transmission by a convulsant benzodiazepine. J Pharmacol Exp Ther 211:290–295, 1979.
Armbrecht HJ, Wood WG, Wise RW et al: Ethanol-induced disordering of membranes from different age groups of C57BL/6NNIA mice. J Pharmacol Exp Ther 226:387–391, 1983.
Harris RA, Crabbe JC, McSwigan JD: Relationship of membrane physical properties to alcohol dependence in mice selected for genetic differences in alcohol withdrawal. Life Sci 35:2601–2608, 1984.
Harris RA, Bruno P: Membrane disordering by anesthetic drugs: Relationship to synaptosomal sodium and calcium fluxes. J Neurochem 44:1274–1281, 1985.
Michaelis ML, Michaelis EK, Tehan T: Alcohol effects on synaptic membrane calcium ion fluxes. Pharmacol Biochem Behav 18(suppl 1):19–23, 1983.
Nachshen DA, Blaustein MP: Some properties of potassium-stimulated calcium influx in presynaptic nerve terminals. J Gen Physiol 76:709–728, 1980.
Katz B, Miledi R: A study of synaptic transmission in the absence of nerve impulses. J Physiol (Lond) 192:407–436, 1967.
Katz B, Miledi R: The timing of calcium action during neuromuscular transmission. J Physiol (Lond) 189:535–544, 1967.
Douglas WW, Rubin RP: The mechanism of catecholamine release from the adrenal medulla and the role of calcium in stimulus secretion coupling. J Physiol (Lond) 167:288–310, 1963.
Heyer EJ, MacDonald RL: Calcium-and sodium-dependent action potentials of mouse spinal cord and dorsal root ganglion neurons in cell culture. J Neurophysiol 47:641–655, 1982.
Leslie SW, Barr E, Chandler LJ: Comparison of voltage-dependent 45Ca2+ uptake rates by synaptosomes isolated from rat brain regions. J Neurochem 41:1602–1605, 1983.
Llinas R, Nicholson C: Calcium role in depolarization-secretion coupling: An aequorin study in squid giant synapse. Proc Natl Acad Sci USA 72:187–190, 1975.
Schweitzer ES, Blaustein MP: Calcium buffering in presynaptic nerve terminals: Free calcium levels measured with arsenazo III. Biochim Biophys Acta 600:912–921, 1980.
Ashley RH, Brammer MJ, Marchbanks R: Measurement of intrasynaptosomal free calcium by using the fluorescent indicator quin-2. Biochem J 219:149–158, 1984.
Blaustein MP, Johnson EM, Needleman P: Calcium-dependent norepinephrine release from presynaptic nerve endings in vitro. Proc Natl Acad Sci USA 69:2237–2240, 1972.
Blaustein MP, Ratzlaff RW, Kendrick NC, et al: Calcium buffering in presynaptic nerve terminals. I. Evidence for involvement of a nonmitochondrial ATP-dependent sequestration mechanism. J Gen Physiol 72:15–41, 1978.
Blaustein MP, Russell JM: Sodium-calcium exchange and calcium-calcium exchange in internally dialyzed squid giant axons. J Membr Biol 22:285–312, 1975.
Drapeau P, Blaustein MP: Initial release of [3H]dopamine from rat striatal synaptosomes: Correlation with calcium entry. J Neurosci 3:703–713, 1983.
Suszkiw JB, O’leary ME: Temporal characteristics of potassium-stimulated acetylcholine release and inactivation of calcium influx in rat brain synaptosomes. J Neurochem 41:868–873, 1983.
Floor E: Substance P release from K+-depolarized rat brain synaptosomes at one-second resolution. Brain Res 279:321–324, 1983.
Leslie SW, Woodward JJ, Wilcox RE: Correlation of rates of calcium entry and endogenous dopamine release in mouse striatal synaptosomes. Brain Res 325:99–105, 1985.
Turner TJ, Goldin SM: Calcium channels in rat brain synaptosomes: Identification and pharmacological characterization: High affinity blockade by organic Ca2+ channel blockers. J Neurosci 5:841–849, 1985.
Blaustein MP, Ector AC: Barbiturate inhibition of calcium uptake by depolarized nerve terminals in vitro. Mol Pharmacol 11:369–378, 1975.
Friedman MB, Erickson CK, Leslie SW: Effects of acute and chronic ethanol administration on whole mouse brain synaptosomal calcium influx. Biochem Pharmacol 29:1903–1908, 1980.
Harris RA, Hood WF: Inhibition of synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 213:562–567, 1980.
Hood WF, Harris RA: Effects of depressant drugs and sulfhydryl reagents on the transport of calcium by isolated nerve terminals. Biochem Pharmacol 29:957–959, 1980.
Leslie SW, Friedman MB, Wilcox RE, et al: Acute and chronic effects of barbiturates on depolarization-induced calcium influx into rat synaptosomes. Brain Res 185:409–417, 1980.
Elrod SV, Leslie SW: Acute and chronic effects of barbiturates on depolarization-induced calcium influx into synaptosomes from rat brain regions. J Pharmacol Exp Ther 212:131–136, 1980.
Stokes JA, Harris RA: Alcohols and synaptosomal calcium transport. Mol Pharmacol 22:99–104, 1982.
Oakes SG, Pozos RS: Electrophysiological effects of ethanol on dissociated sensory ganglia in vitro. Alcoholism Clin Exp Res 4:225, 1980.
Eskuri S, Pozos R: Development of ethanol tolerance in sensory neurons in culture. Alcoholism Clin Exp Res 9:197, 1985.
Triestman SN, Camacho-Nasi P, Wilson A: Alcohol effects on voltage-dependent currents in identified cells. Alcoholism Clin Exp Res 9:201, 1985.
Leslie SW, Barr E, Chandler J, et al: Inhibition of fast-and slow-phase depolarization-dependent synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 225:571–575, 1983.
Leslie SW, Barr EM, Chandler LJ, et al: Sedative-hypnotic drugs and synaptosomal calcium transport, in Rubin RP, Weiss GB, Putney JW (eds): Calcium in Biological Systems. New York, Plenum Press, 1985, pp 221–226.
Okamoto M: Barbiturates and alcohol: Comparative overviews on neurophysiology and neurochemistry, in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of Progress. New York, Raven Press, 1978, pp 1575–1590.
Ondrusek MG, Belknap JK, Leslie SW: Effects of acute and chronic barbiturate administration on synaptosomal calcium accumulation. Mol Pharmacol 15:386–395, 1979.
Janis RA, Scriabine A: Sites of action of Ca2+ channel inhibitors. Biochem Pharmacol 32:3499–3507, 1983.
Ehlert FJ, Roeske WR, Itoga E, et al: The binding of [3H] nitrendipine to receptors for calcium channel antagonists in the heart, cerebral cortex, and ileum of rats. Life Sci 30:2191–2202, 1982.
Bellemann P, Schade A, Towart R: Dihydropyridine receptor in rat brain labeled with [3H]nimodipine. Proc. Natl Acad Sci USA 80:2356–2360, 1983.
Gould RJ, Murphy KMM, Snyder SH: Tissue heterogeneity of calcium channel antagonist binding sites labeled by [3H]nitrendipine. Mol Pharmacol 25:235–241, 1984.
Nachshen DA, Blaustein MP: The effects of some organic calcium antagonists on calcium influx in presynaptic nerve terminals. Mol Pharmacol 16:579–586, 1979.
Daniell LC, Barr EM, Leslie SW: 45Ca2+ uptake into rat whole brain synaptosomes unaltered by dihydropyridine calcium antagonists. J Neurochem 41:1455–1459, 1983.
Middlemiss DN, Spedding M: A functional correlate for the dihydropyridine binding site in rat brain. Nature 314:94–96, 1985.
Hoffmeister F, Benz U, Heise A, et al: Behavioral effects of nimodipine in animals. Drug Res 32:347–360, 1982.
Itil TM, Michael ST, Hoffmeister F, et al: Nimodipine, a calcium antagonist vasodilator with psychotropic properties (a controlled quantitative pharmaco-EEG study). Curr Ther Res 35:405–422, 1984.
Isaacson RL, Molina JC, Draski LI, et al: Nimodipine’s interactions with other drugs. I. Ethanol. Life Sci 36:2195–2199, 1985.
Greenberg DA, Cooper EC: Effect of ethanol on [3H]nitrendipine binding to calcium channels in brain membranes. Alcoholism Clin Exp Res 8:568–571, 1984.
Harris RA, Jones SB, Bruno P, et al: Effects of dihydropyridine derivatives and anticonvulsant drugs on [3H]nitrendipine binding and calcium and sodium fluxes. Biochem Pharmacol 34:2187–2191, 1985.
Morgan KG, Bryant SH: Pentobarbital: Presynaptic effect in the squid giant synapse. Experientia 33:487–488, 1977.
Kleinhaus AL, Prichard JW: Interaction of divalent cations and barbiturates on four identified leech neurons. Comp Biochem Physiol 63C:351–357, 1979.
Heyer EC, MacDonald RL: Barbiturate reduction of calcium-dependent action potentials: Correlation with anesthetic action. Brain Res 236:157–171, 1982.
Goldring JM, Blaustein MP: Effect of pentobarbital on Na and Ca action potentials in an invertebrate neuron. Brain Res 240:273–283, 1982.
Nishi K, Oyama Y: Barbiturates increase the rate of voltage-dependent inactivation of the calcium current in snail neurones. Br J Pharmacol 80:761–765, 1983.
Pincus JH, Hsiao K: Calcium uptake mechanisms affected by some convulsant and anticonvulsant drugs. Brain Res 217:119–127, 1981.
Harris RA, Stokes JA: Effects of a sedative and a convulsant barbiturate on synaptosomal calcium transport. Brain Res 242:157–163, 1982.
Holtman JR, Richter JA: Comparison of the in vivo effects of convulsant and optically active hypnotic barbiturates with their effects on the in vitro K+-stimulated release of [3H]acetylcholine. Biochem Pharmacol 30:2619, 1981.
Holtman JR, Richter JA: Increased release of [3H]acetylcholine in vitro from the mouse hippocampus by a convulsant barbiturate. Neuropharmacology 22:1101–1108, 1983.
Chandler LJ, Leslie SW, Gonzales R: 5-(2-Cyclohexylideneethyl)-5-ethyl-barbituric acid (CHEB): Correlation of hypnotic and convulsant properties with alterations of synaptosomal 45Ca2+ influx. Eur J Pharmacol 126:117–123, 1986.
Leslie SW, Friedman MB, Coleman RR: Effects of chlordiazepoxide on depolarization-induced calcium influx into synaptosomes. Biochem Pharmacol 29:2439–2443, 1980.
Ferrendelli JA, Daniels-McQueen S: Comparative actions of phenytoin and other anticonvulsant drugs on potassium-and veratridine-stimulated calcium uptake in synptosomes. J Pharmacol Exp Ther 220:29–34, 1982.
Taft WC, DeLorenzo RJ: Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations. Proc Natl Acad Sci USA 81:3118–3122, 1984.
Johansen J, Taft WC, Yang J, et al: Inhibition of Ca2+ conductance in identified leech neurons by benzodiazepines. Proc Natl Acad Sci USA 82:3935–3939, 1985.
Skerritt JH, Werz MA, McLean MJ, et al: Diazepam and its anomalous p-chloro-derivative Ro5-4864: Comparative effects on mouse neurons in cell culture. Brain Res 310:99–105, 1984.
Harris RA: Ethanol and pentobarbital inhibition of intrasynaptosomal sequestration of calcium. Biochem Pharmacol 30:3209–3215, 1981.
Yamamoto H-A, Harris RA: Effects of ethanol and barbiturates on Ca2+-ATPase activity of erythrocyte and brain membranes. Biochem Pharmacol 32:2787–2791, 1983.
Michaelis ML, Michaelis EK: Alcohol and local anesthetic effects on Na+-dependent Ca2+ fluxes in brain synaptic membrane vesicles. Biochem Pharmacol 32:963–969, 1983.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Springer Science+Business Media New York
About this chapter
Cite this chapter
Leslie, S.W. (1987). Calcium Channels. In: Galanter, M. (eds) Recent Developments in Alcoholism. Recent Developments in Alcoholism, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1684-6_10
Download citation
DOI: https://doi.org/10.1007/978-1-4899-1684-6_10
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-1686-0
Online ISBN: 978-1-4899-1684-6
eBook Packages: Springer Book Archive