Charge movement and calcium currents in skeletal muscle fibers are enhanced by GTP gamma S

Abstract

G-proteins play several regulatory roles in the cell. They can modulate ionic channels directly or in association with second messengers. In skeletal muscle, G-proteins modulate the activity of calcium channels either by acting directly on the channel and/or through a cAMP-dependent phosphorylating mechanism. The activation of G-proteins by GTP gamma S can also induce force generation in skinned fibers. In this paper we studied the effect of GTP gamma S on charge movement and calcium currents (ICa) in rat and frog skeletal muscle, using the Vaseline gap technique. We observed an increase in both charge movement and ICa after the intracellular addition of 10-100 microM GTP gamma S. GDP beta S did not have any effect. Addition of protein kinase A catalytic subunit increased the ICa, probably through a phosphorylation process, but did not modify the charge movement. This suggests that protein kinase A and GTP gamma S are acting on different sites of the channel. It can be speculated that G-proteins may have a regulatory role in the excitation-contraction coupling mechanism by a direct effect on charge movement.