CAFFEINE INDUCES PERIODIC OSCILLATIONS OF CA2-ACTIVATED K+ CURRENT INPULMONARY ARTERIAL SMOOTH-MUSCLE CELLS()

The periodic oscillations of outward currents were studied in smooth m uscle cells of the rabbit pulmonary artery. The combined stimuli of su perfusion with 1 mM caffeine and depolarization of the membrane potent ial to O mV evoked periodic oscillations of outward currents with fair ly uniform amplitudes and intervals. The oscillating outward currents induced by caffeine were dependent on intracellular Ca2+ concentration ([Ca2+](i)) and had a reversal potential near to the equilibrium pote ntial for K+. So the oscillating outward currents are carried by K+ th rough Ca2+-dependent K+ channels (I-K(Ca)), and may reflect the oscill ations of [Ca2+](i). The oscillating outward currents were abolished, or their frequency reduced, by lowering external [Ca2+], Ca2+ channel blockers, or by 1 mu M ryanodine, indicating that: (1) there is a cont inuous influx of Ca2+ through the plasma membrane at a holding potenti al of O mV; (2) the periodic transient increases of [Ca2+](i) are ascr ibed to the rhythmic release of Ca2+ from ryanodine-sensitive intracel lular store by the mechanism of Ca(2+)induced CA(2+) release (CICR). O n the basis of the above results, we simulated the oscillation of [Ca2 +](i) induced by caffeine, which is known to lower the threshold of CI CR. The patterns of peak amplitude histograms of spontaneous transient outward currents (STOC) in the oscillating cells were different from those in non-oscillating cells. The amplitudes of STOC in the latter w ere more variable than those in the former. The oscillating outward cu rrents were modulated by 1 mu M forskolin and 1 mu M sodium nitropruss ide, but STOC were little affected. The above differences between STOC and oscillating outward currents suggest that the two currents are ac tivated by the Ca2+ originating from different intracellular Ca2+ stor es which are functionally heterogeneous.