• Muscle Contraction C1-C6 PC1-PC11

University of Heidelberg (2006) Proc Physiol Soc 4, PC8

Poster Communications: Zoita Andronache1, Daniel Ursu1, Marc Freichel2, Veit Flockerzi2, Werner Melzer1

1. Angewandte Physiologie, University of Ulm, Ulm, Germany. 2. Experimentelle und Klinische Pharmakologie und Toxikologie, Universitat des Saarlandes, Homburg, Germany.

Adult skeletal muscle fibres of mice lacking the DHP receptor γ1-subunit exhibit changes of voltage dependence of inactivation of both Ca2+ conductance and sarcoplasmic reticulum Ca2+ release. The steady state inactivation curves were found to be shifted to more positive potentials indicating that γ1 favours the inactivated state of the voltage sensor (Ursu et al. 2004). These effects of the γ1-subunit resemble the effect reported for certain Ca2+ channel antagonists on excitation-contraction coupling (e.g. Erdmann & Lüttgau, 1989) raising the possibility of a common modulatory mechanism. We performed experiments in single voltage-clamped interosseus fibres and measured the voltage-activated Ca2+ release flux by analysing fura-2 fluorescence signals (Ursu et al. 2005) to determine whether wild type (γ1+/+) and γ1-null (γ1-/-) muscles differ from each other with respect to their sensitivity to the phenylalkylamine L-type Ca2+ channel antagonist (-)D888. We studied the time course of recovery from inactivation of Ca2+ release flux in the presence of different concentration of (-)D888. Inactivation was caused by a depolarising voltage step to +10 mV lasting 60 s. Recovery was assessed at different holding potentials using 100 ms depolarising test pulses to +20 mV. (-)D888 caused a substantial concentration-dependent slowing of recovery and left shift of the voltage dependence of recovery both in γ1-/- and γ1+/+ fibres. In γ1-/- fibres the voltages of half-maximum recovery (V1/2) at quasi steady state (190 s after inactivation) in the presence of 0, 5 and 10 µM (-)D888 were -36, -49 and -55 mV, respectively. In γ1+/+ fibres V1/2 values were -47, -67 and -69 mV, respectively. In γ1-/- muscle fibres, 5 µM (-)D888 reversed the effect of γ1-subunit deficiency underlining the Ca2+ antagonist-like modulation of voltage-controlled Ca2+ release by this auxiliary subunit. Moreover, in γ1+/+ fibres the effect of (-)D888 on recovery was enhanced which may point to a positive allosteric interaction of the subunit with the phenylalkylamine binding site.

View other abstracts by:

• Ursu, D
• Freichel, M
• Flockerzi, V
• Melzer, W
• Andronache, Z