A novel calcium current in dysgenic skeletal muscle

Abstract

The whole-cell patch-clamp technique was used to study voltagedependent calcium currents in primary cultures of myotubes and in freshly dissociated skeletal muscle from normal and dysgenic mice. In addition to the transient, dihydropyridine (DHP)-insensitive calcium current previously described, a maintained DHP-sensitive calcium current was found in dysgenic skeletal muscle. This current, here termed Ica-dys, is largest in acutely dissociated fetal or neonatal dysgenic muscle and also in dysgenic myotubes grown on a substrate of killed fibroblasts. In dysgenic myotubes grown on untreated plastic culture dishes, Ica-dys is usually so small that it cannot be detected. In addition, Ica-dys is apparently absent from normal skeletal muscle. From a holding potential of -80 mV, Ica-dys a becomes apparent for test pulses to -- 20 mV and peaks at - + 20 mV. The current activates rapidly (rise time ~5 ms at 20°C) and with 10 mM Ca as charge cattier inactivates little or not at all during a 200-ms test pulse. Thus, Ica-dys - activates much faster than the slowly activating calcium current of normal skeletal muscle and does not display Ca-dependent inactivation like the cardiac L-type calcium current. Substituting Ba for Ca as the charge carrier doubles the size of Ica-dys without altering its kinetics. Ica-dys is ~75% blocked by 100 nM (+)-PN 200-110 and is increased about threefold by 500 nM racemic Bay K 8644. The very high sensitivity of Ica-dys, to these DHP compounds distinguishes it from neuronal L-type calcium current and from the calcium currents of normal skeletal muscle. Ica-dys may represent a calcium channel that is normally not expressed in skeletal muscle, or a mutated form of the skeletal muscle slow calcium channel. © 1989, Rockefeller University Press., All rights reserved.