Non‐invasive magnetic resonance imaging assessment of myocardial changes and the effects of angiotensin‐converting enzyme inhibition in diabetic rats

Abstract

Calcium channels are essential for excitation-contraction coupling and muscle development. At the end of fetal life, two types of Ca²⁺ currents can be recorded in muscle cells. Whereas L-type Ca²⁺ channels have been extensively studied, T-type channels have been poorly characterized in skeletal muscle. We describe here the functional and molecular properties of T-type calcium channels in developing mouse skeletal muscle. The T-type current density increased transiently during prenatal myogenesis with a maximum at embryonic day E16 followed by a drastic decrease until birth. This current showed similar electrophysiological and pharmacological properties at all examined stages. It displayed a wide window current centred at about −35 and −55 mV in 10 and 2 mm external Ca²⁺, respectively. Activation and inactivation kinetics were fast (3 and 16 ms, respectively). The current was inhibited by nickel and amiloride with an IC₅₀ of 5.4 and 156 μm, respectively, values similar to those described for cloned T-type α_1H channels. Whole muscle tissue RT-PCR analysis revealed mRNAs corresponding to α_1H and α_1G subunits in the fetus but not in the adult. However, single-fibre RT-PCR demonstrated that only α_1H mRNA was present in prenatal fibres, suggesting that the α_1G transcript present in muscle tissue must be expressed by non-skeletal muscle cells. Altogether, these results demonstrate that the α_1H subunit generates functional T-type calcium channels in developing skeletal muscle fibres and suggest that these channels are involved in the early stages of muscle differentiation.