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Sci. Signal., 30 March 2010
Vol. 3, Issue 115, p. ec92
[DOI: 10.1126/scisignal.3115ec92]


Evolution When a Channel Is Not a Channel

Nancy R. Gough

Science Signaling, AAAS, Washington, DC 20005, USA

Excitation-contraction (EC) coupling is the process by which an electrical signal triggers muscle contraction. Depolarization activates a voltage-gated Ca2+ channel (Cav), which activates an intracellular calcium channel (RyR), releasing sufficient calcium to trigger muscle contraction. In the mammalian heart, Cav1.2 channels conduct Ca2+, and this increase in Ca2+ concentration contributes to the activation of the RyR. In mammalian skeletal muscle, the Cav1.1 channel only conducts a very small and slowly activating current, and the RyR is activated by a direct interchannel coupling mechanism. Schredelseker et al. investigated excitation-contraction coupling in teleost fish. Whole-cell patch clamp analysis revealed that myotubes from zebrafish larvae did not have a voltage-dependent inward Ca2+ current but did exhibit gating currents specific to Cav1.1 channels. (Gating currents represent the movement of the voltage-sensing residues and indicate a conformational change in the channel.) Depolarization stimulated an increase in intracellular Ca2+ concentration consistent with RyR release of Ca2+ and EC coupling. By searching the zebrafish genome, the authors found two genes encoding the {alpha} subunit of the Cav1.1 channel (Cav1.1{alpha}1S), but each of these exhibited mutations predicted to block Ca2+ conduction. Expression of zf-{alpha}1S-a or zf-{alpha}1S-b in {alpha} subunit–deficient mouse myotubes (derived from a cell line) showed that these channels failed to conduct Ca2+ but were competent for EC coupling. Introduction of these mutations into rabbit Cav1.1{alpha}1S rendered that channel incapable of Ca2+ conduction. Each of the two genes was selectively expressed in a particular type of muscle fiber in the adult zebrafish. Transcripts for zf-{alpha}1S-a, along with RyR1a, were abundant in slow fibers involved in persistent swimming. Transcripts for zf-{alpha}1S-b, along with RyR1b, were abundant in fast fibers involved in burst swimming. Analysis of the sequences of Cav1.1 channels from 32 species of teleost fish (17 different orders) showed that all of them had channels with conductance-blocking mutations. The authors suggest that the earliest forms of EC coupling involved Ca2+-conducting Ca2+ channels; then conformational coupling arose, leading to a combination of mechanisms of RyR activation, with some species (teleost fish) bearing mutations that resulted in complete loss of calcium conduction.

J. Schredelseker, M. Shrivastav, A. Dayal, M. Grabner, Non-Ca2+-conducting Ca2+ channels in fish skeletal muscle excitation-contraction coupling. Proc. Natl. Acad. Sci. U.S.A. 107, 5658–5663 (2010). [Abstract] [Full Text]

Citation: N. R. Gough, When a Channel Is Not a Channel. Sci. Signal. 3, ec92 (2010).

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