Decreased voltage dependent K+ currents in cerebral arterial smooth muscle cells of one-kidney, one-clip Goldblatt hypertensive rat

ABSTRACT

The Kv channel activity in vascular smooth muscle cell plays an important role in the regulation of membrane potential and blood vessel tone. It was postulated that increased blood vessel tone in hypertension was associated with alteration of Kv channel and membrane potential. Therefore, using whole cell mode of patch-clamp technique, the membrane potential and the 4-AP-sensitive Kv current in cerebral arterial smooth muscle cells were compared between normotensive rat and one-kidney, one-clip Goldblatt hypertensive rat (1K,1C-GBH rat). Cell capacitance of hypertensive rat was similar to that of normotensive rat. Cell capacitance of normotensive rat and 1K,1C-GBH rat were 20.8+/-2.3 and 19.5+/-1.4 pF, respectively. The resting membrane potentials measured in current clamp mode from normotensive rat and 1K,1C-GBH rat were -45.9+/-1.7 and -38.5+/-1.6 mV, respectively. 4-AP (5 mM) caused the resting membrane potential hypopolarize but charybdotoxin (0.1 muM) did not cause any change of membrane potential. Component of 4-AP-sensitive Kv current was smaller in 1K,1C-GBH rat than in normotensive rat. The voltage dependence of steady-state activation and inactivation of Kv channel determined by using double-pulse protocol showed no significant difference. These results suggest that 4-AP-sensitive Kv channels play a major role in the regulation of membrane potential in cerebral arterial smooth muscle cells and alterations of 4-AP-sensitive Kv channels would contribute to hypopolarization of membrane potential in 1K,1C-GBH rat.