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Differential effects of voltage-dependent inactivation and local anesthetics on kinetic phases of Ca2+ release in frog skeletal muscle.

Abstract：

:In voltage-clamped frog skeletal muscle fibers, Ca(2+) release rises rapidly to a peak, then decays to a nearly steady state. The voltage dependence of the ratio of amplitudes of these two phases (p/s) shows a maximum at low voltages and declines with further depolarization. The peak phase has been attributed to a component of Ca(2+) release induced by Ca(2+), which is proportionally greater at low voltages. We compared the effects of two interventions that inhibit Ca(2+) release: inactivation of voltage sensors, and local anesthetics reputed to block Ca(2+) release induced by Ca(2+). Holding the cells partially depolarized strongly reduced the peak and steady levels of Ca(2+) release elicited by a test pulse and suppressed the maximum of the p/s ratio at low voltages. The p/s ratio increased monotonically with test voltage, eventually reaching a value similar to the maximum found in noninactivated fibers. This implies that the marked peak of Ca(2+) release is a property of a cooperating collection of voltage sensors rather than individual ones. Local anesthetics reduced the peak of release flux at every test voltage, and the steady phase to a lesser degree. At variance with sustained depolarization, they made p/s low at all voltages. These observations were well-reproduced by the "couplon" model of dual control, which assumes that depolarization and anesthetics respectively, and selectively, disable its Ca(2+)-dependent or its voltage-operated channels. This duality of effects and their simulation under such hypotheses are consistent with the operation of a dual, two-stage control of Ca(2+) release in muscle, whereby Ca(2+) released through multiple directly voltage-activated channels builds up at junctions to secondarily open Ca(2+)-operated channels.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Brum G,Piriz N,DeArmas R,Rios E,Stern M,Pizarro G

doi

10.1016/S0006-3495(03)74470-1

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

245-54

issue

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(03)74470-1

journal_volume

pub_type

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Differential effects of voltage-dependent inactivation and local anesthetics on kinetic phases of Ca2+ release in frog skeletal muscle.