CRITICAL ROLES OF THE S3 SEGMENT AND S3-S4 LINKER OF REPEAT-I IN ACTIVATION OF L-TYPE CALCIUM CHANNELS

被引:92
作者
NAKAI, J
ADAMS, BA
IMOTO, K
BEAM, KG
机构
[1] COLORADO STATE UNIV,COLL VET MED & BIOMED SCI,DEPT PHYSIOL,FT COLLINS,CO 80523
[2] KYOTO UNIV,FAC MED,DEPT MED CHEM,KYOTO 606,JAPAN
关键词
DIHYDROPYRIDINE RECEPTOR; HEART; SKELETAL MUSCLE;
D O I
10.1073/pnas.91.3.1014
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Each of the four repeats (or motifs) of voltage-gated ion channels is thought to contain six transmembrane segments (S1-S6). Mutational analyses indicate that S4 functions as a voltage sensor and that the S5, S6, and S5-S6 linker contribute to formation of the ion pore. However, little information exists regarding the functional role(s) of the amino-terminal portion (S1-S3-S4 linker) of the repeats. Here we report that the amino acid composition of the S3 segment of repeat I and the linker connecting S3 and S4 segments of repeat I is critical for the difference in activation kinetics between cardiac and skeletal muscle L-type calcium channels. Mutant dihydropyridine receptors that have the skeletal muscle dihydropyridine receptor sequence in this region activated relatively slowly with the time constant of current activation (tau(act)) > 5 ms, whereas mutants that have the cardiac counterpart there activated relatively rapidly with tau(act) < 5 ms. Comparison of these two mutant groups indicates that a total of 11 conservative and 10 nonconservative amino acid changes from skeletal muscle to cardiac dihydropyridine receptor sequence are sufficient to convert activation from slow to fast. These data demonstrate a functional role for this region of voltage-gated ion channels.
引用
收藏
页码:1014 / 1018
页数:5
相关论文
共 35 条
[1]  
ADAMS B A, 1992, Biophysical Journal, V61, pA419
[2]   INTRAMEMBRANE CHARGE MOVEMENT RESTORED IN DYSGENIC SKELETAL-MUSCLE BY INJECTION OF DIHYDROPYRIDINE RECEPTOR CDNAS [J].
ADAMS, BA ;
TANABE, T ;
MIKAMI, A ;
NUMA, S ;
BEAM, KG .
NATURE, 1990, 346 (6284) :569-572
[3]   A NEUTRAL AMINO-ACID CHANGE IN SEGMENT-IIS4 DRAMATICALLY ALTERS THE GATING PROPERTIES OF THE VOLTAGE-DEPENDENT SODIUM-CHANNEL [J].
AULD, VJ ;
GOLDIN, AL ;
KRAFTE, DS ;
CATTERALL, WA ;
LESTER, HA ;
DAVIDSON, N ;
DUNN, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (01) :323-327
[4]   A LETHAL MUTATION IN MICE ELIMINATES THE SLOW CALCIUM CURRENT IN SKELETAL-MUSCLE CELLS [J].
BEAM, KG ;
KNUDSON, CM ;
POWELL, JA .
NATURE, 1986, 320 (6058) :168-170
[5]   CALCIUM CURRENTS IN EMBRYONIC AND NEONATAL MAMMALIAN SKELETAL-MUSCLE [J].
BEAM, KG ;
KNUDSON, CM .
JOURNAL OF GENERAL PHYSIOLOGY, 1988, 91 (06) :781-798
[6]   CLASSES OF CALCIUM CHANNELS IN VERTEBRATE CELLS [J].
BEAN, BP .
ANNUAL REVIEW OF PHYSIOLOGY, 1989, 51 :367-384
[7]   THE BIOCHEMISTRY AND MOLECULAR-BIOLOGY OF THE DIHYDROPYRIDINE-SENSITIVE CALCIUM-CHANNEL [J].
CAMPBELL, KP ;
LEUNG, AT ;
SHARP, AH .
TRENDS IN NEUROSCIENCES, 1988, 11 (10) :425-430
[8]  
CASTELLANO A, 1993, J BIOL CHEM, V268, P3450
[9]   STRUCTURE AND FUNCTION OF VOLTAGE-SENSITIVE ION CHANNELS [J].
CATTERALL, WA .
SCIENCE, 1988, 242 (4875) :50-61
[10]  
CHAUDHARI N, 1992, J BIOL CHEM, V267, P25636