BK channels

demonstrated that maternal diabetes reduced the excitability and increased small conductance Ca2+-activated K+ (SK) currents of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA). In addition, blockade of SK channels with apamin completely abolished this reduction. In this study, we examined whether maternal diabetes affects large conductance Ca2+-activated K+ (BK) channels and whether BK channels contribute to the attenuation of PCMN excitability observed in offspring of diabetic mothers. Neonatal mice from OVE26 diabetic mothers (NMDM) and normal FVB mothers (control) were used. The pericardial sac of neonatal mice at P7-9 was injected with the tracer XRITC two days prior to the experiment to retrogradely label PCMNs in the NA. Whole-cell voltage and current clamps were used to measure spike frequency, action potential (AP) repolarization (half-width), afterhyperpolarization potential (AHP), transient outward currents and afterhyperpolarization currents (IAHP...

Dopamine, a key neurotransmitter mediating the rewarding properties of drugs of abuse, is widely believed to exert some of its effects by modulating neuronal activity of nucleus accumbens (NAcc) medium spiny neurons (MSNs). Although its effects on synaptic transmission have been well documented, its regulation of intrinsic neuronal excitability is less understood. In this study, we examined the cellular mechanisms of acute dopamine effects on core accumbens MSNs evoked firing. We found that 0.5 µM A-77636 and 10 µM quinpirole, dopamine D1 (DR1s) and D2 receptor (D2Rs) agonists, respectively, markedly inhibited MSN evoked action potentials. This effect, observed only in about 25% of all neurons, was associated with spike-timing-dependent (STDP) long-term potentiation (tLTP), but not long-term depression (tLTD). Dopamine inhibits evoked firing by compromising subthreshold depolarization, not by altering action potentials themselves. Recordings in voltage-clamp mode revealed that all M...

Large-conductance Ca2+-activated K+ (BK) channels are reported to be essential for NADPH oxidase-dependent microbial killing and innate immunity in leukocytes. Using human peripheral blood and mouse bone marrow neutrophils, pharmacological targeting, and BK channel gene-deficient (BK−/−) mice, we stimulated NADPH oxidase activity with 12- O-tetradecanoylphorbol-13-acetate (PMA) and performed patch-clamp recordings on isolated neutrophils. Although PMA stimulated NADPH oxidase activity as assessed by O2− and H2O2 production, our patch-clamp experiments failed to show PMA-activated BK channel currents in neutrophils. In our studies, PMA induced slowly activating currents, which were insensitive to the BK channel inhibitor iberiotoxin. Instead, the currents were blocked by Zn2+, which indicates activation of proton channel currents. BK channels are gated by elevated intracellular Ca2+ and membrane depolarization. We did not observe BK channel currents, even during extreme depolarizatio...

Hydrogen sulfide (H2S) is a key signalling molecule regulating important physiological processes, including smooth muscle function. However, the mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are not well understood. This study investigates the cellular and tissue mechanisms by which H2S regulates DSM contractility, excitatory neurotransmission, and large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels in freshly-isolated guinea pig DSM. We used a multidisciplinary experimental approach including isometric DSM tension recordings, colorimetric ACh measurement, Ca(2+) imaging, and patch-clamp electrophysiology. In isolated DSM strips, the novel slow release H2S donor, P-(4-methoxyphenyl)-p-4-morpholinylphosphinodithioic acid morpholine salt (GYY4137), significantly increased the spontaneous phasic and nerve-evoked DSM contractions. The blockade of neuronal voltage-gated Na(+) channels or muscarinic ACh receptors with tetrodotoxin or atropine, ...