Voltage-dependent inward currents in smooth muscle cells of skeletal muscle arterioles

Voltage-dependent inward currents responsible for the depolarizing phase of action potentials were characterized in smooth muscle cells of 4(th) order arterioles in mouse skeletal muscle. Currents through L-type Ca(2+) channels were expected to be dominant; however, action potentials were not eliminated in nominally Ca(2+)-free bathing solution or by addition of L-type Ca(2+) channel blocker nifedipine (10 μM). Instead, Na(+) channel blocker tetrodotoxin (TTX, 1 μM) reduced the maximal velocity of the upstroke at low, but not at normal (2 mM), Ca(2+) in the bath. The magnitude of TTX-sensitive currents recorded with 140 mM Na(+) was about 20 pA/pF. TTX-sensitive currents decreased five-fold when Ca(2+) increased from 2 to 10 mM. The currents reduced three-fold in the presence of 10 mM caffeine, but remained unaltered by 1 mM of isobutylmethylxanthine (IBMX). In addition to L-type Ca(2+) currents (15 pA/pF in 20 mM Ca(2+)), we also found Ca(2+) currents that are resistant to 10 μM nifedipine (5 pA/pF in 20 mM Ca(2+)). Based on their biophysical properties, these Ca(2+) currents are likely to be through voltage-gated T-type Ca(2+) channels. Our results suggest that Na(+) and at least two types (T- and L-) of Ca(2+) voltage-gated channels contribute to depolarization of smooth muscle cells in skeletal muscle arterioles. Voltage-gated Na(+) channels appear to be under a tight control by Ca(2+) signaling.