DECREASED SMALL CONDUCTANCE, CALCIUM‐ACTIVATED POTASSIUM (SK) CURRENT UNDERLIES INCREASED EXCITABILITY OF PVN‐RVLM NEURONS AND SYMPATHOEXCITATION IN ANG II‐SALT HYPERTENSIVE (HT) RATS

Abstract

A neural mechanism responsible for sympathoexcitation in HT rats was investigated. We hypothesized that reduced SK current in PVN neurons projecting to RVLM (PVN‐RVLM) could contribute to increased excitability and sympathetic outflow in HT rats. In voltage‐clamp recordings, the amplitude of SK current in neurons from HT rats (12±6 pA, n=5) was significantly (p<0.01) less than that from neurons of normotensive (NT) rats (73±12 pA, n=5). In current‐clamp recordings, graded current injections evoked graded increases in discharge frequency. Maximum discharge was evoked by +200 pA injections in neurons from HT rats (47±5 Hz, n=10). This response was significantly greater (P<0.001) than that of neurons from NT rats (25±2 Hz, n=10). The SK channel blocker UCL1684 (100 nM) significantly increased (p<0.05) discharge in neurons from NT rats (39±4 Hz, n=6), but had no effect on neurons from HT rats (46±2 Hz, n=10). The contribution of SK channel activity in regulating ongoing sympathetic activity was assessed by microinjecting UCL1684 into the PVN of anesthetized rat. UCL1684 significantly (P<0.05) increased RSNA by 58±14 % and MAP by 10±1 mmHg in NT rats (n=4), but was without effect in HT rats (n=4). We conclude that increased excitability of PVN‐RVLM neurons may contribute to sympathoexcitation and maintenance of hypertension. Reduced SK current in these neurons may constitute an underlying neural mechanism. Support: AHA0865107F (QHC) & HL076312 (GMT)