SMALL CONDUCTANCE CALCIUM‐ACTIVATED POTASSIUM CHANNELS (SK) LIMIT THE EXCITABILITY OF PVN NEURONS PROJECTING TO RVLM (PVN‐RVLM)

Abstract

In vivo studies indicate that under normal condition pre‐autonomic PVN neurons are often silent or have low spontaneous activity. In spite of their importance in regulating sympathetic outflow, mechanisms that control the excitability of pre‐autonomic PVN neurons remain largely unexplored. Here, we determined the role of SK channels in limiting excitability of PVN‐RVLM neurons. In voltage‐clamp recordings, an outward current (IK) (amplitude: 72 ± 10 pA; decay constant: 234 ± 55 ms, n=8) was nearly abolished by the SK channel blocker apamin or UCL1684. Activation of IK was Ca2+ dependent and reversed at ‐97±3 mV (n=3) which was close to the EK value (‐103 mV). In current‐clamp recordings, graded current injections evoked graded increases in spike frequency. Maximum discharge was evoked by +200 pA injections and averaged 22 ± 3 Hz (n=8) and was significantly greater (P<0.05) in the presence of apamin (100 nM) (47 ± 8 Hz, n=8) or UCL1684 (100 nM) (39 ± 5, n=5). Apamin and UCL1684 each blocked a prominent medium after hyperpolarization potential (mAHP: ‐11 ± 2 mV) that was evident in response to current injection. With blockade of the mAHP, a prominent after depolarization potential (ADP) was revealed (amplitude: apamin +9 ± 1; UCL1684 +7 ± 2 mV). We conclude that SK channel activation limits the excitability of PVN‐RVLM neurons. An underlying mechanism may be the ability of the mAHP to oppose the ADP. Support: AHA0865107F (QHC) & HL076312 (GMT)