A reduction in SK channels contributes to increased activity of hypothalamic magnocellular neurons during heart failure

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12507-list-0001">Small conductance Ca²⁺‐activated K⁺ (SK) channels play an important role in regulating the excitability of magnocellular neurosecretory cells (MNCs). Although an increased SK channel function contributes to adaptive physiological responses, it remains unknown whether changes in SK channel function/expression contribute to exacerbated MNC activity under disease conditions.We show that the input–output function of MNCs in heart failure (HF) rats is enhanced. Moreover, the SK channel blocker apamin enhanced the input–output function in sham, although not in HF rats.We found that both the after‐hyperpolarizing potential magnitude and the underlying apamin‐sensitive I AHP are blunted in MNCs from HF rats.The magnitude of spike‐induced increases in intracellular Ca²⁺ levels was not affected in MNCs of HF rats.We found a diminished expression of SK2/SK3 channel subunit mRNA expression in the supraoptic nucleus of HF rats.Our studies suggest that a reduction in SK channel expression, but not changes in Ca²⁺‐mediated activation of SK channels, contributes to exacerbated MNC activity in HF rats.