HYPOXIA INCREASES THE ACTIVITY OF CA2-SENSITIVE K+ CHANNELS IN CAT CEREBRAL ARTERIAL MUSCLE-CELL MEMBRANES()

The cellular mechanisms mediating hypoxia-induced dilation of cerebral arteries have remained unknown, but may involve modulation of membran e ionic channels. The present study was designed to determine the effe ct of reduced partial pressure of O-2, PO2, on the predominant K+ chan nel type recorded in cat cerebral arterial muscle cells, and on the di ameter of pressurized cat cerebral arteries. A K+-selective single-cha nnel current with a unitary slope conductance of 215 pS was recorded f rom excised inside-out patches of cat cerebral arterial muscle cells u sing symmetrical KCl (145 mM) solution. The open state probability (NP o) of this channel displayed a strong voltage dependence, was not affe cted by varying intracellular ATP concentration [(ATP](i)) between 0 a nd 100 mu M, but was significantly increased upon elevation of intrace llular free Ca2+ concentration ([Ca2+](i)). Low concentrations of exte rnal tetraethylammonium (0.1-3 mM) produced a concentration-dependent reduction of the unitary current amplitude of this channel. In cell-at tached patches, where the resting membrane potential was set to zero w ith a high KCl solution, reduction of O-2 from 21% to < 2% reversibly increased the NPo, mean open time, and event frequency of the Ca2+-sen sitive, high-conductance single-channel K+ current recorded at a patch potential of + 20 mV. A similar reduction in PO2 also produced a tran sient increase in the activity of the 215-pS K+ channel measured in ex cised inside-out patches bathed in symmetrical 145 mM KCl, an effect w hich was diminished, or not seen, during a second application of hypox ic superfusion. Hypoxia had no effect on [Ca2+](i) of intracellular pH (pH(i))) of cat cerebral arterial muscle cells, as measured using Ca2 +- or pH-sensitive fluorescent probes. Reduced PO2 caused a significan t dilation of pressurized cerebral arterial segments, which was attenu ated by pretreatment with 1 mM tetraethylammonium. These results sugge st that reduced PO2 increases the activity of a high-conductance, Ca2-sensitive K+ channel in cat cerebral arterial muscle cells, and that these effects are mediated by cytosolic events independent of changes in [Ca2+](i) and pH(i).