Effects of guanidinium on EC coupling and tension generation in frog skeletal muscle.

The effect of the chaotropic cation guanidinium on tension generation was investigated in voltage-clamped intact and mechanically skinned muscle fibres of the frog. When sodium was replaced by guanidinium in the solution a 20-mV shift of the sigmoidal activation curve towards less negative potentials was recorded. A similar shift in the voltage dependence of mechanical inactivation did not occur. The plateau phase of contractures activated by long-lasting depolarizations was significantly shortened in the presence of 77.5 mM guanidinium. In a second set of experiments, charge displacement currents were measured using the cut fibre preparation. Apparently, guanidinium had no effect on the voltage dependence of intramembrane charge movement. On the other hand, this cation caused a distinct increase in the amount of charge necessary to reach the contraction threshold at rheobase voltage from 12.4nC microF-1 to 23.4nC microF-1. Experiments on skinned fibres containing an operating sarcoplasmic reticulum demonstrated that 5 mM guanidinium diminished caffeine-induced tension development and substantially delayed the onset of the contractile response. However, guanidinium did not impair calcium-induced tension development of the contractile apparatus. These results suggest that the inhibitory action of guanidinium on excitation-contraction coupling is due to a depression of calcium release from the sarcoplasmic reticulum.