SPONTANEOUS TRANSIENT INWARD CURRENTS AND RHYTHMICITY IN CANINE AND GUINEA-PIG TRACHEAL SMOOTH-MUSCLE CELLS

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 nifed ipine. Ca2+-activated K+ currents often preceded STICs, suggesting tha t the STICs are Ca2+ dependent. In support of this suggestion, we foun d 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- c urrent are of small unitary conductance (<20 pS). Decay of the STICs w as 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 Ca2+-dependent Cl- currents and contractions as indi ces of internal levels of Ca2+, we found that isolated tracheal cells are capable of exhibiting rhythmic behaviour: bursts of currents and c ontractions 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 s equestered Ca2+ is responsible. We conclude that spontaneous release o f Ca2+ from intracellular stores in tracheal muscle cells leads to tra nsient currents in some cases accompanied by rhythmic contractions. Ou r studies provide evidence for a cellular mechanism that could underly myogenic oscillations of membrane potential in smooth muscle.