ACTION OF CAFFEINE ON TRANSMEMBRANE POTAS SIUM CURRENTS IN SINGLE SMOOTH-MUSCLE CELLS FROM GUINEA-PIG MESENTERIC-ARTERY

Whole-cell transmembrane outward currents evoked by Ca2+ release from caffeine-sensitive intracellular stores in isolated smooth muscle cell s from guinea-pig mesenteric artery were investigated using patch-clam p method. Application of caffeine during voltage stepping from - 70 mV to 10 mV was followed by high-amplitude outward current consisting of fast and slow components whose rates of rise and fall differed marked ly. Both components were carried by K+ ions and could be blocked by TE A with equal efficiency. Recovery of the fast component was found to b e faster than that of the slow one and could be detected 50 s after ca ffeine removal. In contrast, the spontaneous transient outward current s (STOC) were restored in 1-2 s suggesting that Ca2+ release from Ca2-sensitive stores is not related to STOCs activation. Caffeine was fou nd to block the voltage sensitive transient K+ current, while TEA-sens itive Ca2+-activated K channels were resistant to caffeine. Our data s upport the suggestion that STOC's and both components of the caffeine- induced K+ current are carried through identical Ca2+-activated K chan nels that differ in location and the sources of activator Ca2+. STOCs and the fast component are carried through the same K channels located in the region of narrow gaps between the membrane and superficial sar coplasmic reticulums (SR), but activator Ca2+ ions enter the gap from extracellular space in the first case or are released from SR in the s econd case. The slow component is activated by Ca2+ ions released from deep SR.