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Small‐conductance Ca 2+ ‐activated K + (SK) channels regulate pre‐sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) and parasympathetic cardiomotor neurons (CMN) in the nucleus ambiguus (NA): Pathological changes
Author(s) -
Cheng Zixi,
Lin Ming,
Toney Glenn M.,
Chen Qinghui
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.718.5
Subject(s) - rostral ventrolateral medulla , apamin , chemistry , afterhyperpolarization , neuroscience , medicine , brainstem , depolarization , endocrinology , sk channel , patch clamp , medulla oblongata , electrophysiology , potassium channel , central nervous system , biology , ion channel , receptor
SK channels regulate action potential (AP) firing patterns and neuronal excitability in a Ca 2+ dependent manner. Here, we report on (1) the functional role of SK channels in pre‐sympathetic neurons of the PVN and parasympathetic CMN of the NA and (2) the pathological contributions of SK channels in salt‐sensitive hypertension (SSH), maternal diabetes (MD) and chronic intermittent hypoxia (CIH). For PVN : Whole cell patch‐clamp recordings were made in brain slices from PVN neurons retrogradely labelled from the rostral ventrolateral medulla (RVLM). In current‐clamp recordings, we found that depolarizing current injections evoked action potentials that underwent spike‐frequency adaptation (SFA). Bath application of apamin increased PVN‐RVLM neuronal excitability, while attenuating current evoked SFA and the amplitude of the ensuing after hyperpolarization potential (AHP). In voltage‐clamp recordings, step depolarization elicited a Ca 2+ ‐dependent delayed outward current ( I AHP ) that temporally corresponded to the AHP. I AHP was nearly abolished by the SK channel blocker apamin. Neurons from rats with SSH had diminished SK currents and enhanced excitability, which reflected reduced SFA and diminished AHP amplitude. Collectively, these data indicate that SK channels in PVN‐RVLM neurons play an important role in regulating excitability and suggest that diminished SK channel current in SSH could lead to increased neuronal discharge and thereby contribute to sympathoexcitation in this model of neurogenic hypertension. For CMN: The tracer XRITC was injected into the pericardial space to label parasympathetic CMN in mice. Two days later, whole cell recordings were made from labeled CMN in brainstem slices. In current‐clamp recordings, depolarizing current injections evoked spike trains that underwent SFA. Bath application of apamin increased neuronal excitability, abolished SFA and suppressed the amplitude of the AHP. In voltage clamp recordings, a Ca 2+ ‐dependent, apamin‐sensitive I AHP was identified. In mice with MD and mice exposed to CIH, the apamin sensitive I AHP was enhanced and excitability was reduced, suggesting that SK channels negatively regulate AP discharge of CMN and could contribute to impaired vagal baroreflex control of the heart in these disease models. Ongoing studies in disease models seek to determine mechanisms to explain why SK channel function is diminished in PVN pre‐sympathetic neurons but enhanced in NA parasympathetic neurons. Support or Funding Information Support: HL‐79636 (ZC), HL‐088052 (GMT) and HL‐122952 (QHC).