Cellular mechanism of force development in cat middle cerebral artery by reducedPCO₂

Abstract

These studies were undertaken to determine the effect of reducing aPCO₂ below physiological levels on cat middle cerebral artery. Upon reduction ofPCO₂ from 37 to 14 torr (pH 7.4) we observed membrane depolarization and force development. ReducingPCO₂ decreased the slope of theE _m vs. log [K]_o curve and increased the slope of the steady-state I/V relationship suggesting that the change inE _m was due to reduction of outward K⁺ conductance (g _k). 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 theE _m vs. log [K]_o curve) and increasing the slope of the I/V relationship to statistically equivalent values as reduction ofPCO₂. ReturningPCO₂ 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 elevatingPCO₂ in cerebral arteries. The response to changing pH_o followed a slower time course but did not change with time. These studies demonstrate that both elevated pH_o and reducedPCO₂ activate cerebral arterial muscle by a mechanism which includes reduction ing _k. However, it can not be determined if these similar responses and reduction, ofg _k are mediated by changing pH_i or mediated through different mechanisms. It is possible that pH_o andPCO₂ can modify cerebral arterial tone by direct mechanisms and not necesarily by their effect on pH_i. It is clear, however, that reduction ofPCO₂ and elevation of pH_o both activate cerebral arterial muscle by a mechanism which includes reduction ofg _k.