ANNUAL REVIEWS Annu. Rev. Neurosci. 1990. 13:337-56 Copyright © 1990 by Annual Reviews Inc. All rights reserved
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CALCIUM CHANNELS IN
Annu. Rev. Neurosci. 1990.13:337-356. Downloaded from www.annualreviews.org Access provided by Iowa State University on 01/29/19. For personal use only.
VERTEBRATE CELLS Peter Hess Department of Cellular and Molecular Physiology, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115 INTRODUCTION Ca channels are transmembrane proteins that in the open conformation allow the passive flux of Ca ions across the membrane, down the elec trochemical gradient. In this review I deal only with voltage-activated, Ca selective channels in the surface membrane, and restrict the discussion largely to Ca channels in vertebrates. I concentrate on new insights into the functional molecular properties revealed by single channel recording techniques, on structural information gained by biochemical and molec ular biological techniques, and on newly recognized pathways ofCa chan nel modulation. For a historical account of the discovery of Ca permeability, the reader should consult previous reviews (Reuter 19 73, Hagiwara & Byerly 1981, Kostjuk 1981, Tsien 1983). By focusing on the elementary properties of Ca channels, I also fall short of a description of the many important physiological roles of Ca channels. The various aspects of the control of intracellular Ca in neurons, including the role played by neuronal Ca channels, have recently been discussed in a special issue of Trends in Neuroscience (see Tsien et al 1988). Voltage-sensitive Ca channels are found in most cell types studied today (for review see Bean 1989a), and are not restricted to classically excitable cells like neurons, muscle, and heart. One of the significant advances in the understanding of Ca channels in recent years has been the realization that most cell membranes contain several types of voltage-activated Ca channels, which can be classified according to their biophysical properties and pharmacological sensitivities. 337 0147-006X/90/0301-0337$02. 00
Annu. Rev. Neurosci. 1990.13:337-356. Downloaded from www.annualreviews.org Access provided by Iowa State University on 01/29/19. For personal use only.
3 38
HESS
The Skeletal Muscle Dihydropyridine Receptor l , 4-dihydropyridine (DHP) Ca channel ligands have been used extensively to study DHP-sensitive Ca channels (for review see Janis et a1198 7, Hosey & Lazdunski 1988). DHP receptors are found in T-tubular membranes from skeletal muscle at a density 50-100 times higher than in any other tissue (Fosset et a1 198 3 , Glossman et al 198 3). Skeletal muscle has there fore been used as the source for successful solubilization and purification of the DHP receptor. Initial reports described a single large subunit of 150170 kDa and several smaller ones ranging from 30-50 kDa (Glossmann & Ferry 1983, Curtis & Catterall 1984, Borsotto et al 1984, 1985). More recently, several laboratories have demonstrated that two large subunits, c
Further
Quick links to online content
CALCIUM CHANNELS IN
Annu. Rev. Neurosci. 1990.13:337-356. Downloaded from www.annualreviews.org Access provided by Iowa State University on 01/29/19. For personal use only.
VERTEBRATE CELLS Peter Hess Department of Cellular and Molecular Physiology, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115 INTRODUCTION Ca channels are transmembrane proteins that in the open conformation allow the passive flux of Ca ions across the membrane, down the elec trochemical gradient. In this review I deal only with voltage-activated, Ca selective channels in the surface membrane, and restrict the discussion largely to Ca channels in vertebrates. I concentrate on new insights into the functional molecular properties revealed by single channel recording techniques, on structural information gained by biochemical and molec ular biological techniques, and on newly recognized pathways ofCa chan nel modulation. For a historical account of the discovery of Ca permeability, the reader should consult previous reviews (Reuter 19 73, Hagiwara & Byerly 1981, Kostjuk 1981, Tsien 1983). By focusing on the elementary properties of Ca channels, I also fall short of a description of the many important physiological roles of Ca channels. The various aspects of the control of intracellular Ca in neurons, including the role played by neuronal Ca channels, have recently been discussed in a special issue of Trends in Neuroscience (see Tsien et al 1988). Voltage-sensitive Ca channels are found in most cell types studied today (for review see Bean 1989a), and are not restricted to classically excitable cells like neurons, muscle, and heart. One of the significant advances in the understanding of Ca channels in recent years has been the realization that most cell membranes contain several types of voltage-activated Ca channels, which can be classified according to their biophysical properties and pharmacological sensitivities. 337 0147-006X/90/0301-0337$02. 00
Annu. Rev. Neurosci. 1990.13:337-356. Downloaded from www.annualreviews.org Access provided by Iowa State University on 01/29/19. For personal use only.
3 38
HESS
The Skeletal Muscle Dihydropyridine Receptor l , 4-dihydropyridine (DHP) Ca channel ligands have been used extensively to study DHP-sensitive Ca channels (for review see Janis et a1198 7, Hosey & Lazdunski 1988). DHP receptors are found in T-tubular membranes from skeletal muscle at a density 50-100 times higher than in any other tissue (Fosset et a1 198 3 , Glossman et al 198 3). Skeletal muscle has there fore been used as the source for successful solubilization and purification of the DHP receptor. Initial reports described a single large subunit of 150170 kDa and several smaller ones ranging from 30-50 kDa (Glossmann & Ferry 1983, Curtis & Catterall 1984, Borsotto et al 1984, 1985). More recently, several laboratories have demonstrated that two large subunits, c
