Cellular mechanism of force development in cat middle cerebral artery by reduced PCO2

These studies were undertaken to determine the effect of reducing a PCO2 below physiological levels on cat middle cerebral artery. Upon reduction of PCO2 from 37 to 14 torr (pH 7.4) we observed membrane depolarization and force development. Reducing PCO2 decreased the slope of the Em vs. log [K]o curve and increased the slope of the steady-state I/V relationship suggesting that the change in Em was due to reduction of outward K+ conductance (gk). Elevation of pH from 7.37 to 7.6 had a very similar effect on these cerebral arterial muscle cells, depolarizing the muscle membrane (reducing the Em vs. log [K]o curve) and increasing the slope of the I/V relationship to statistically equivalent values as reduction of PCO2. Returning PCO2 from 14 to 37 torr rapidly relaxed these preparations, but only transiently. This relaxation was followed by a rebound contraction within 3 min, demonstrating a transient nature for the action of elevating PCO2 in cerebral arteries. The response to changing pHo followed a slower time course but did not change with time. These studies demonstrate that both elevated pHo and reduced PCO2 activate cerebral arterial muscle by a mechanism which includes reduction in gk. However, it can not be determined if these similar responses and reduction of gk are mediated by changing pHi or mediated through different mechanisms. It is possible that pHo and PCO2 can modify cerebral arterial tone by direct mechanisms and not necessarily by their effect on pHi. It is clear, however, that reduction of PCO2 and elevation of pHo both activate cerebral arterial muscle by a mechanism which includes reduction of gk.