Chronic intermittent hypoxia decreases acute hypoxic inhibition of voltage-gated potassium channel in rat pulmonary arterial smooth muscle cells / 生理学报

ABSTRACT

For determination the ionic mechanisms of the hypoxic acclimatization at the level of channels, male Spradue-Dawley rats were divided into two groups control normoxic group and chronic intermittent hypoxic group [O2 concentration (10 +/-0.5)%, hypoxia 8 h a day]. Using whole cell patch-clamp technique, voltage-gated potassium channel currents (IK(V)) were recorded in freshly isolated pulmonary arterial smooth muscle cells (PASMCs) of rat with acute isolated method. The effect of acute hypoxia on IK(V) of PASMCs from chronic intermittent hypoxia group was investigated to offer some basic data for clarifying the ionic mechanisms of the hypoxic acclimatization. The results showed (1) In control normoxic group, after acute hypoxia free-Ca(2+) solution, the resting membrane potential (Em) of PASMCs was depolarized significantly from -47.2+/-2.6 mV to -26.7+/-1.2 mV, and the IK(V) of PASMCs was decreased significantly from 153.4+/-9.5 pA/pF to 70.1+/-0.6 pA/pF, the peak current percent inhibition was up to (57.6+/-3.3)% at +60 mV, and current-voltage relationship curve shifted to the right. (2) In chronic intermittent hypoxic group, the IK(V) of PASMCs was decreased significantly by exposure to intermittent hypoxia in a time-dependent manner, appeared to start on day 10 and continued to day 30 (the longest time tested) of hypoxia, and current-voltage relationship curve shifted to the right in a time-dependent manner. (3) Compared with the control normoxic group, the percent IK(V) inhibition by acute hypoxia was significantly attenuated in the chronic intermittent hypoxia group and this inhibition effect declined with time exposure to hypoxia. The results suggest that K(V) inhibition was significantly attenuated by chronic intermittent hypoxia, and this effect may be a critical mechanism of the body hypoxic acclimatization.