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Research Paper

The cardiac α_1C subunit can support excitation-triggered Ca²⁺ entry in dysgenic and dyspedic myotubes

Roger A. Bannister and Kurt Beam

Depolarization-induced entry of divalent ions into skeletal muscle has been attributed to a process termed Excitation-Coupled Ca²⁺ Entry (ECCE), which is hypothesized to require the interaction of the ryanodine receptor (RyR1), the L-type Ca²⁺ 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 Mn²⁺ quench of Fura-2, is reconstituted by expression of a mutant DHPR α_1S subunit (SkEIIIK) thought to be impermeable to divalent cations. Previously, we showed that the bulk of depolarization-induced Ca²⁺ entry could be explained by the skeletal L-type current. Accordingly, one would predict that any Ca²⁺ 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 α_1C subunit in either dysgenic or dyspedic myotubes does result in Ca²⁺ entry similar to that ascribed to ECCE. We also demonstrate that, when potentiated by strong depolarization and Bay K 8644, SkEIIIK supports entry of Mn²⁺. These results strongly support the idea that the L-type channel is the major route of Ca²⁺ entry in response to repetitive or prolonged depolarization of skeletal muscle.

Authors

Roger A. Bannister

University of Colorado, Denver

Kurt Beam Corresponding author: Kurt.Beam@uchsc.edu

University of Colorado Health Science Center