Objective: 

The Ca²⁺ conducting transient receptor potential (TRP) channels TRPC3 and C6 have been suggested to contribute to the abnormal Ca²⁺ regulation in mdx muscle. To address this question we tested the effect of the TRP channel blocker 2-aminoethoxydiphenyl borate (2-APB) and the activator of TRPC3/C6 and C7 channels 1-oleoyl-2-acetyl-sn-glycerol (OAG) on resting Ca²⁺ influx and KCl-induced Ca²⁺ transients.

Methods: 

Background Ca²⁺ influx of M. interosseus fibres was judged by the manganese-quench technique. Decline of Fura-2 fluorescence was studied in the presence of 0.5 mM Mn²⁺ and the quench rate (in % per min) during the first 10 minutes after Mn²⁺ application was evaluated. KCl induced Ca-transients were recorded using the Ca²⁺-indicator Fura-2.

Results: 

Under standard conditions a quench rate of Fura-2 of 3.9 ± 0.34 (n = 59) was observed in wildtype fibres. In the presence of 150 mM OAG the rate was higher (+ 34 %) while application of 50 mM 2-APB resulted in a significantly lower rate of 2.3 ± 0.27 (n = 44). Though the basal quench rate was higher in mdx fibers than in controls we did not observe significant changes in response to 2-APB or OAG. The decay of KCl-induced Ca-transients (measured as half-time of decay) was significantly decreased by 12.2 % after 2-APB application in wildtype fibres. This effect was likewise not detectable in mdx fibres. Application of OAG did not affect half-time of decay neither in wildtype nor in mdx muscle fibres.

Conclusion: 

The cation channels TRPC3 and/or C6 seem to contribute to background Ca²⁺ influx in wildtype muscle fibres. In mdx fibres their contribution is much lower or even absent. Thus, TRPC3 and -C6 do not account for the increased background Ca²⁺ current observed in mdx muscle. Reduced TRPC3/C6 expression or function may be a compensatory effect in response to the increased intracellular Ca²⁺ level in dystrophic muscle.