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Department of Biochemistry, Cinvestav-IPN, AP 14-740, Mexico City, DF 07000, Mexico

In skeletal muscle myogenesis, precursor cells or myoblasts fuse to form multinucleated cells (myotubes), which then further develop into functional muscle. We investigated if the inhibition of myogenesis by transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2) involve regulation of voltage-dependent Ca²⁺ channels. Primary cultured myoblasts were kept in fusion medium (0–6 days) in either the absence (control conditions) or the presence of 40 pM TGF-ß1 or 5 nM BMP-2. Subsequently, the developing myotubes were transferred to a growth factor-free recording solution, and subjected to whole cell patch-clamp experiments. At day 0, 14% of non-fusing myoblasts exhibited T-current, whereas the L-current was practically absent. Under control conditions, however, the percentage of T- and L-channel-expressing myotubes increased sharply, from 25% at day 1 to 100% at days 2–6. In addition, parallel increases were determined for Ca²⁺-currents density and cell membrane capacitance (C_m), which is proportional to the size of myotubes. Interestingly, at days 1–2 TGF-ß1 and BMP-2 eliminated the T-current on initial 14% of T-channel-expressing myoblasts. Moreover, at day 6 the growth factors significantly reduced the maximal values of both T-current density (80%) and C_m (60%). The effect of BMP-2 was selective on T-channels, whereas TGF-ß1 decreased also the L-current density (90%). A similar reduction in maximal conductance of the Ca²⁺ channels was determined, in the absence of significant alterations in other essential properties of the channels, including the time course and voltage dependence of activation and inactivation. The results suggest these growth factors markedly reduce the number of functional T- (both TGF-ß1 and BMP-2) and L-channels (only TGF-ß1) in the surface of the plasma membrane, and contribute to explaining the associated effects on myogenesis.

(Received 20 April 2004; accepted after revision 14 June 2004; first published online 24 June 2004)
Corresponding author G. Avila: Department of Biochemistry, Cinvestav-IPN, AP 14-740, Mexico City, DF 07000, Mexico. Email: gavila{at}mail.cinvestav.mx

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