Molecular Origin of the L-Type Ca.sup.2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor [beta].sub.1a Subunit

Caroline Strube; Maryline Beurg; Manana Sukhareva; Chris A Ahern; Jeanne A Powell; Patricia A Powers; Ronald G Gregg; Roberto Coronado

doi:10.1016/S0006-3495(98)77507-1

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Molecular Origin of the L-Type Ca.sup.2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor [beta].sub.1a Subunit

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Molecular Origin of the L-Type Ca.sup.2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor [beta].sub.1a Subunit

Caroline Strube, Maryline Beurg, Manana Sukhareva, Chris A Ahern, Jeanne A Powell, Patricia A Powers, Ronald G Gregg and Roberto Coronado

Biophysical journal, Vol.75(1), p.207

07/01/1998

DOI: 10.1016/S0006-3495(98)77507-1

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Abstract

The origin of I.sub.[beta]null, the Ca.sup.2+ current of myotubes from mice lacking the skeletal dihydropyridine receptor (DHPR) [beta].sub.1a subunit, was investigated. The density of I.sub.[beta]null was similar to that of I.sub.dys, the Ca.sup.2+ current of myotubes from dysgenic mice lacking the skeletal DHPR [alpha].sub.1S subunit (-0.6[+ or -]0.1 and -0.7[+ or -]0.1 pA/pF, respectively). However, I.sub.[beta]null activated at significantly more positive potentials. The midpoints of the G.sub.Ca-V curves were 16.3[+ or -]1.1mV and 11.7[+ or -]1.0mV for I.sub.[beta]null and I.sub.dys, respectively. I.sub.[beta]null activated significantly more slowly than I.sub.dys. At +30mV, the activation time constant for I.sub.[beta]null was 26[+ or -]3ms, and that for I.sub.dys was 7[+ or -]1ms. The unitary current of normal L-type and [beta].sub.1-null Ca.sup.2+ channels estimated from the mean variance relationship at +20mV in 10mM external Ca.sup.2+ was 22[+ or -]4 fA and 43[+ or -]7 fA, respectively. Both values were significantly smaller than the single-channel current estimated for dysgenic Ca.sup.2+ channels, which was 84[+ or -]9 fA under the same conditions. I.sub.[beta]null and I.sub.dys have different gating and permeation characteristics, suggesting that the bulk of the DHPR [alpha].sub.1 subunits underlying these currents are different. I.sub.[beta]null is suggested to originate primarily from Ca.sup.2+ channels with a DHPR [alpha].sub.1S subunit. Dysgenic Ca.sup.2+ channels may be a minor component of this current. The expression of DHPR [alpha].sub.1S in [beta].sub.1-null myotubes and its absence in dysgenic myotubes was confirmed by immunofluorescence labeling of cells.

Muscles

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Title: Subtitle: Molecular Origin of the L-Type Ca.sup.2+ Current of Skeletal Muscle Myotubes Selectively Deficient in Dihydropyridine Receptor [beta].sub.1a Subunit
Creators: Caroline Strube
Maryline Beurg
Manana Sukhareva
Chris A Ahern - University of Iowa, Molecular Physiology and Biophysics
Jeanne A Powell
Patricia A Powers
Ronald G Gregg
Roberto Coronado
Resource Type: Journal article
Publication Details: Biophysical journal, Vol.75(1), p.207
DOI: 10.1016/S0006-3495(98)77507-1
ISSN: 0006-3495
eISSN: 1542-0086
Publisher: Elsevier B.V
Language: English
Date published: 07/01/1998
Description audience: Academic
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984070229802771

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