Deletion of amino acids 1641-2437 from the foot region of skeletal muscle ryanodine receptor alters the conduction properties of the Ca release channel.

Abstract:

:The ryanodine receptor (RyR) of skeletal muscle contains two functional domains: a carboxyl-terminal hydrophobic domain that forms the putative conduction pore of the calcium release channel, and a large cytoplasmic domain that corresponds to the "foot structure." To understand the contribution of the foot structure to the function of the calcium release channel, we studied a RyR deletion mutant, delta(1641-2437)-RyR, in which a region that is rich in glutamate and aspartate residues (a.a. 1641-2437) was removed. The wild-type and delta(1641-2437)-RyR proteins were expressed in a Chinese hamster ovary (CHO) cell line, and functions of single calcium release channels were measured in the lipid bilayer membrane. The wild-type RyR forms functional calcium release channels with a linear current-voltage relationship similar to that of the native channel identified in the sarcoplasmic reticulum membrane of skeletal muscle, whereas the channels formed by delta(1641-2437)-RyR exhibit significant inward rectification, i.e., currents moving from cytoplasm into SR lumen were approximately 20% less than that in the opposite direction. As in to the wt-RyR channel, opening of the delta(1641-2437)-RyR channel has a bell-shaped dependence on the cytoplasmic calcium, but the calcium-dependent activation and inactivation processes of the delta(1641-2437)-RyR channel are shifted to higher calcium concentrations. Our data show that deletion of a.a. 1641-2437 from the foot region of the skeletal muscle RyR results in changes in both ion conduction and calcium-dependent regulation of the calcium release channel.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Bhat MB,Zhao J,Hayek S,Freeman EC,Takeshima H,Ma J

doi

10.1016/S0006-3495(97)78165-7

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

1320-8

issue

3

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(97)78165-7

journal_volume

73

pub_type

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