Ca2+ entry through acetylcholine receptor channel in dysgenic myotubes.

Abstract

Skeletal muscles of mutant mice with "muscular dysgenesis" are characterized by excitation-contraction uncoupling resulting from the absence of dihydropyridine receptors. However contraction of the dysgenic myotubes can be evoked by afferent nerve stimulation or by ionophoretic application of acetylcholine (ACh) on the muscle. These contractions are elicited by Ca2+ entry through the ionic channel of the ACh receptor at multiple synaptic contacts. In the present paper, the calcium entry through ACh receptors was compared in cultured normal and dysgenic myotubes. At elevated external calcium concentration (110 mM), the elementary slope conductance of the ACh-activated ionic channel of dysgenic myotubes did not differ from that found in normal myotubes. We conclude that dysgenic muscle contraction induced by nerve stimulation does not result from an abnormal Ca2+ entry across ACh receptors. We discuss the possible involvement of sustained high threshold calcium current (Idys) and of the calcium induced calcium release mechanism in the contractile response related to synaptic activity of dysgenic myotubes.