Characteristics of single large-conductance Ca2+-activated K+ channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus
Abbreviated Journal Title
J. Mod. Eur. Hist.
nucleus ambiguus; parasympathetic cardiac motoneurons; vagal; BK; channels; repolarization; afterhyperpolarization; firing frequency; adaptation; ACTIVATED POTASSIUM CHANNEL; RAT HIPPOCAMPAL-NEURONS; CHRONIC; INTERMITTENT HYPOXIA; SPIKE FREQUENCY ADAPTATION; HEART-RATE CONTROL; AFTER-HYPERPOLARIZATION; SYMPATHETIC NEURONS; PYRAMIDAL CELLS; BAROREFLEX SENSITIVITY; NEURAL DEGENERATION; Cell Biology; Physiology
Large-conductance Ca2+-activated K+ channels (BK) regulate action potential (AP) properties and excitability in many central neurons. However, the properties and functional roles of BK channels in parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) have not yet been well characterized. In this study, the tracer Xrhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal 7-9 days. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. Using excised patch single-channel recordings, we identified voltage-gated and Ca2+-dependent BK channels in PCMNs. The majority of BK channels exhibited persistent channel opening during voltage holding. These BK channels had a conductance of 237 pS and a 50% opening probability at +27.9 mV, the channel open time constant was 3.37 ms at +20 mV, and dwell time increased exponentially as the membrane potential depolarized. At the +20-mV holding potential, the [Ca2+](50) was 15.2 mu M with a P-0.5 of 0.4. Occasionally, some BK channels showed a transient channel opening and fast inactivation. Using whole cell voltage clamp, we found that BK channel mediated outward currents and afterhyperpolarization currents (I-AHP). Using whole cell current clamp, we found that application of BK channel blocker iberiotoxin (IBTX) increased spike half-width and suppressed fast afterhyperpolarization (fAHP) amplitude following single APs. In addition, IBTX application increased spike half-width and reduced the spike frequency-dependent AP broadening in trains and spike frequency adaption (SFA). Furthermore, BK channel blockade decreased spike frequency. Collectively, these results demonstrate that PCMNs have BK channels that significantly regulate AP repolarization, fAHP, SFA, and spike frequency. We conclude that activation of BK channels underlies one of the mechanisms for facilitation of PCMN excitability.
M. Lin; J. T. Hatcher; R. D. Wurster; Q. H. Chen;Z. X. Cheng
"Characteristics of single large-conductance Ca2+-activated K+ channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus" (2014). Faculty Bibliography 2010s. 5700.