Pharmacology, structure and function of cardiac L-type Ca2+ channels

被引:141
作者
Striessnig, J [1 ]
机构
[1] Inst Biochem Pharmacol, A-6020 Innsbruck, Austria
关键词
Ca2+ channels; heart; biochemistry; modulation;
D O I
10.1159/000016320
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Voltage-gated L-type Ca2+ channels control depolarization-induced Ca2+ entry in different electrically excitable cells, including mammalian heart. Important molecular and functional details providing new insight into L-type channel structure and modulation are reviewed in this article. This includes the identification of amino acid residues responsible for drug binding, the role of accessory subunits and alternative splicing for fine-tuning channel activity and modulation by protein kinases (A, C, tyrosine kinases), cGMP-dependent pathways, calmodulin and Ca2+. Alterations in Ca2+ channel activity under pathological conditions such as in heart failure or during ischemia could provide new clues for the development of drugs to treat cardiovascular diseases. Copyright (C) 1999 S. Karger AG, Basel.
引用
收藏
页码:242 / 269
页数:28
相关论文
共 158 条
[81]   CALCIUM CURRENTS IN VENTRICULAR MYOCYTES OF PREHYPERTROPHIC CARDIOMYOPATHIC HAMSTERS [J].
LI, GR ;
FERRIER, GR ;
HOWLETT, SE .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 268 (03) :H999-H1005
[82]   THE CA CHANNEL IN SKELETAL-MUSCLE IS A LARGE PORE [J].
MCCLESKEY, EW ;
ALMERS, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (20) :7149-7153
[83]   Mibefradil inhibition of T-type calcium channels in cerebellar Purkinje neurons [J].
McDonough, SI ;
Bean, BP .
MOLECULAR PHARMACOLOGY, 1998, 54 (06) :1080-1087
[84]  
MERY PF, 1993, J BIOL CHEM, V268, P26286
[85]   L-TYPE CALCIUM CURRENTS OF HUMAN MYOCYTES FROM VENTRICLE OF NONFAILING AND FAILING HEARTS AND FROM ATRIUM [J].
MEWES, T ;
RAVENS, U .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1994, 26 (10) :1307-1320
[86]   Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca2+ channels [J].
Meyers, MB ;
Puri, TS ;
Chien, AJ ;
Gao, TY ;
Hsu, PH ;
Hosey, MM ;
Fishman, GI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (30) :18930-18935
[87]   ANTAGONISTS OF NEURONAL CALCIUM CHANNELS - STRUCTURE, FUNCTION, AND THERAPEUTIC IMPLICATIONS [J].
MILJANICH, GP ;
RAMACHANDRAN, J .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1995, 35 :707-734
[88]   COORDINATION OF CA2+ BY THE PORE REGION GLUTAMATES IS ESSENTIAL FOR HIGH-AFFINITY DIHYDROPYRIDINE BINDING TO THE CARDIAC CA2+ CHANNEL ALPHA(1) SUBUNIT [J].
MITTERDORFER, J ;
SINNEGGER, MJ ;
GRABNER, M ;
STRIESSNIG, J ;
GLOSSMANN, H .
BIOCHEMISTRY, 1995, 34 (29) :9350-9355
[89]   Identification of PK-A phosphorylation sites in the carboxyl terminus of L-type calcium channel alpha(1) subunits [J].
Mitterdorfer, J ;
Froschmayr, M ;
Grabner, M ;
Moebius, FF ;
Glossmann, H ;
Striessnig, J .
BIOCHEMISTRY, 1996, 35 (29) :9400-9406
[90]   CALCIUM CHANNELS - THE BETA-SUBUNIT INCREASES THE AFFINITY OF DIHYDROPYRIDINE AND CA2+ BINDING-SITES OF THE ALPHA(1)-SUBUNIT [J].
MITTERDORFER, J ;
FROSCHMAYR, M ;
GRABNER, M ;
STRIESSNIG, J ;
GLOSSMANN, H .
FEBS LETTERS, 1994, 352 (02) :141-145