The cardiac alpha(1C) subunit can support excitation-triggered Ca2+ entry in dysgenic and dyspedic myotubes.
Depolarization-induced entry of divalent ions into skeletal muscle has been attributed to a process termed Excitation-Coupled Ca(2+) Entry (ECCE), which is hypothesized to require the interaction of the ryanodine receptor (RyR1), the L-type Ca(2+) channel (DHPR) and another unidentified cation channel. Thus, ECCE is absent in myotubes lacking either the DHPR (dysgenic) or RyR1 (dyspedic). Furthermore, ECCE, as measured by Mn(2+) quench of Fura-2, is reconstituted by expression of a mutant DHPR alpha(1S) subunit (SkEIIIK) thought to be impermeable to divalent cations. Previously, we showed that the bulk of depolarization-induced Ca(2+) entry could be explained by the skeletal L-type current. Accordingly, one would predict that any Ca(2+) current similar to the endogenous current would restore such entry and that this entry would not require coupling to either the DHPR or RyR1. Here, we show that expression of the cardiac alpha(1C) subunit in either dysgenic or dyspedic myotubes does result in Ca(2+) entry similar to that ascribed to ECCE. We also demonstrate that, when potentiated by strong depolarization and Bay K 8644, SkEIIIK supports entry of Mn(2+). These results strongly support the idea that the L-type channel is the major route of Ca(2+) entry in response to repetitive or prolonged depolarization of skeletal muscle.
Bannister
Roger A
RA
Department of Physiology and Biophysics, School of Medicine, University of Colorado-Denver, Aurora, CO, USA.
Beam
Kurt G
KG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism* / Q000502:physiology; D008345:Manganese / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000737:chemistry* / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism* / Q000502:physiology
C514350:CACNA1C protein, mouse; D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D008345:Manganese; D002118:Calcium