Caffeine- and histamine-induced oscillations of K(Ca) current in single smooth muscle cells of rabbit cerebral artery.

In the present experiment, we characterized the intracellular Ca2+ oscillations induced by caffeine (1mM) or histamine (1-3microM) in voltage-clamped single smooth muscle cells of rabbit cerebral (basilar) artery. Superfusion of caffeine or histamine induced periodic oscillations of large whole-cell K+ current with fairly uniform amplitudes and intervals. The oscillatory K+ current was abolished by inclusion of ethylenebis(oxonitrilo)tetraacetate (EGTA, 5mM) in the pipette solution. Caffeine- and histamine-induced periodic activation of the large-conductance Ca2+-activated K+ [K(Ca)] channel was recorded in the cell-attached patch mode. These results suggest that the oscillations of K+ current are carried by the K(Ca) channel and reflect the oscillations of intracellular Ca2+ concentration ([Ca2+]i). Ryanodine (1-10microM) abolished both caffeine- and histamine-induced oscillations. Caffeine-induced oscillations were abolished by the sarcoplasmic reticulum Ca2+-adenosine 5'-triphosphatase (Ca2+-ATPase) inhibitor, cyclopiazonic acid (10microM), and a high concentration of caffeine (10mM). Inclusion of heparin (3mg/ml) in the pipette solution blocked histamine-induced oscillations, but did not block caffeine-induced oscillations. By the removal of extracellular Ca2+, but not by the addition of verapamil and Cd2+, the caffeine-induced oscillations were abolished. Increasing Ca2+ influx rate increased the frequencies of caffeine-induced oscillations. Spontaneous oscillations were also observed in cells that were not superfused with agonists, and had similar characteristics to the caffeine-induced oscillations. From the above results, it is concluded, that in smooth muscle cells of the rabbit cerebral (basilar) artery, ryanodine-sensitive Ca2+-induced Ca2+ release pools play key roles in the generation of caffeine- and histamine-induced intracellular Ca2+ oscillations.