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Inactivation determinants in segment IIIS6 of Ca v 3.1
Author(s) -
Marksteiner R.,
Schurr P.,
Berjukow S.,
Margreiter E.,
PerezReyes E.,
Hering S.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0027k.x
Subject(s) - xenopus , chemistry , alanine , amino acid , mutant , biophysics , kinetics , isoleucine , stereochemistry , biochemistry , biology , leucine , physics , quantum mechanics , gene
1 Low threshold, T‐type, Ca 2+ channels of the Ca v 3 family display the fastest inactivation kinetics among all voltage‐gated Ca 2+ channels. The molecular inactivation determinants of this channel family are largely unknown. Here we investigate whether segment IIIS6 plays a role in Ca v 3.1 inactivation as observed previously in high voltage‐activated Ca 2+ channels. 2 Amino acids that are identical in IIIS6 segments of all Ca 2+ channel subtypes were mutated to alanine (F1505A, F1506A, N1509A, F1511A, V1512A, F1519A, FV1511/1512AA). Additionally M1510 was mutated to isoleucine and alanine. 3 The kinetic properties of the mutants were analysed with the two‐microelectrode voltage‐clamp technique after expression in Xenopus oocytes. The time constant for the barium current ( I Ba ) inactivation, τ inact , of wild‐type channels at −20 mV was 9.5 ± 0.4 ms; the corresponding time constants of the mutants ranged from 9.2 ± 0.4 ms in V1512A to 45.7 ± 5.2 ms (4.8‐fold slowing) in M1510I. Recovery at −80 mV was most significantly slowed by V1512A and accelerated by F1511A. 4 We conclude that amino acids M1510, F1511 and V1512 corresponding to previously identified inactivation determinants in IIIS6 of Ca v 2.1 (Hering et al. 1998) have a significant role in Ca v 3.1 inactivation. These data suggest common elements in the molecular architecture of the inactivation mechanism in high and low threshold Ca 2+ channels.