Spontaneous transient inward currents and rhythmicity in canine and guinea-pig tracheal smooth muscle cells

Abstract

Spontaneous transient inward currents (STICs) were recorded in canine and guinea-pig tracheal myocytes held at negative membrane potentials. STICs were Cl- selective since their reversal potential was dependent on the Cl- gradient and they were blocked by the Cl- channel blocker niflumic acid. STICs were insensitive to Cs+, charybdotoxin, and nifedipine. Ca(2+)-activated K+ currents often preceded STICs, suggesting that the STICs are Ca2+ dependent. In support of this suggestion, we found the Cl- currents were: (1) abolished by depleting intracellular Ca2+ stores using caffeine, acetylcholine, histamine, or substance P; (2) enhanced by increasing external concentrations of Ca2+; (3) evoked by voltage-dependent Ca2+ influx. The channels responsible for this Cl- current are of small unitary conductance (< 20 pS). Decay of the STICs was described by a single exponential with a time constant of 94 +/- 9 ms at -70 mV; the time constant increased considerably at more positive potentials. Using Ca(2+)-dependent Cl- currents and contractions as indices of internal levels of Ca2+, we found that isolated tracheal cells are capable of exhibiting rhythmic behaviour: bursts of currents and contractions with a periodicity of less than 0.1 Hz and which continued for more than 20 min. These rhythmic events were recorded at negative membrane potentials, suggesting that cyclical release of internally sequestered Ca2+ is responsible. We conclude that spontaneous release of Ca2+ from intracellular stores in tracheal muscle cells leads to transient currents in some cases accompanied by rhythmic contractions. Our studies provide evidence for a cellular mechanism that could underly myogenic oscillations of membrane potential in smooth muscle.