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

Abstract

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.