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J Physiol. 2002 Mar 1;539(Pt 2):459-68.

Skeletal muscle L-type Ca(2+) current modulation in gamma1-deficient and wildtype murine myotubes by the gamma1 subunit and cAMP.

Author information

1
Institut für Experimentelle und Klinische Pharmakologie & Toxikologie, Universität des Saarlandes, 66421 Homburg/Saar, Germany. brigette.held@uniklinik-saarland.de

Abstract

Modulation of the steady-state inactivation and current amplitude by the gamma1 subunit of the murine skeletal muscle L-type Ca(2+) channel were investigated using the whole-cell patch-clamp technique. Transient expression of the gamma1 subunit, but not of the gamma2 (stargazin) protein, in primary cultured myotubes from gamma1-deficient mice shifted the steady-state inactivation approximately -15 mV, thereby restoring wildtype (WT) steady-state inactivation and current amplitude. The increased Ca(2+) current amplitude in gamma1-deficient cells was abolished in myotubes from animals of 4 weeks and older whereas the positive shift in steady-state inactivation was independent of mouse age. Raising intracellular cAMP levels using the membrane-permeant analogue 8-Br-cAMP led to an increase in Ca(2+) current amplitude in WT cells to the level in gamma1-deficient myotubes. There was no effect on the current amplitude in gamma1-deficient cells or on the steady-state inactivation in either genotype. Rp-cAMPS, a competitive inhibitor of cAMP-dependent protein kinase, had no effect on the WT Ca(2+) current amplitude and steady-state inactivation, but diminished the current amplitude in gamma1-deficient myotubes without affecting the steady-state inactivation in these cells. These data show that the increased Ca(2+) influx in myotubes lacking the gamma1 subunit, due to right-shifted steady-state inactivation and increased L-type Ca(2+) current amplitude, is determined by the gamma1 subunit. The effect on current amplitude depends on the age of the mice and its cAMP-dependent modulation appears to be controlled by the gamma1 subunit.

PMID:
11882678
PMCID:
PMC2290155
DOI:
10.1113/jphysiol.2001.012745
[Indexed for MEDLINE]
Free PMC Article

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