Abstract 5840: Inhibition of TASK Currents Contributes to Enhanced pH Sensitivity of Chemoreceptors in Prehypertensive SHR
We have demonstrated in glomus cells isolated from carotid bodies of prehypertensive young SHR an enhanced sustained depolarization in response to low pH compared to responses in carotid bodies of WKY rats. A resulting increase in sympathetic activity may contribute to the onset of hypertension. In this experiment we identified a molecular determinant of this enhanced chemoreceptor sensitivity. TASK channels (two-pore-domain, non-voltage gated K+ channels) contribute to an outward leak current which may be inhibited by low pH causing depolarization. Ionic currents were measured in glomus cells isolated from young (4 – 6 weeks) SHR (n=11) and WKY (n=11) rats using the patch-clamp technique. During a slow ramp depolarization of SHR glomus cells from −100 mV to −40 mV the outward current measured at −40 mV was increased to an average value of 12.8±1.4 pA when pH was raised from 7.4 to 8.0, and then progressively decreased with lowering pH to 7.0, 6.5 and 6.0 reaching a low level of 0.0±0.5 pA at pH 6.0. The maximum decline in current (ΔpA) from pH 8.0 to 6.0 which averaged 12.8±1.6 pA in SHR glomus cells was significantly greater than in WKY glomus cells (8.9±1.0 pA). These currents were blocked by quinidine, a known blocker of TASK channels. The enhanced response in SHR was associated with increased expression of TASK1 mRNA (100±17%) and protein (100±48%) in carotid bodies of young SHR (n=4) compared to WKY (n=4). We conclude that hypersensitivity of chemoreceptors in prehypertensive SHR is partly due to overexpression of TASK channels which are sensitive to low pH. The results define a potential genetic determinant of hypertension.