Heterogeneity of conductance states in calcium channels of skeletal muscle.

The single channel conductance of the dihydropyridine (DHP)-sensitive calcium channel from rabbit skeletal muscle transverse tubules was analyzed in detail using the planar bilayer recording technique. With 0.1 M BaCl2 on both sides of the channel (symmetrical solutions), the most frequent conductance is 12 pS, which is independent of holding potential in the range of -80 to +80 mV. This conductance accounts for approximately 80% of all openings analyzed close to 0 mV. Two additional channels of conductance 9 and 3 pS are also present at all positive potentials, but their relative occurrence close to 0 mV is low. All channels depend on the presence of agonist Bay K 8644 and are inhibited by the antagonist nitrendipine. The relative occurrence of 9 and 3 pS can be increased, and that of 12 pS decreased, by several interventions such as external addition of cholesterol, lectin (wheat germ agglutinin), or calmodulin inhibitor R24571 (calmidazolium). The 9- and 3-pS channels are also conspicuous at positive potentials larger than +40 mV. We suggest that 9- and 3-pS channels are two elementary conductances of the same DHP-sensitive Ca channel. Under most circumstances, these two conductances are gated in a coupled way to generate a channel with a unitary conductance of 12 pS. Interventions tested, including large depolarizations, probably decompose or uncouple the 12-pS channel into 9 and 3 pS.