This study examines the roles of voltage-dependent Ca(2+) channels (VDCC), ryanodine receptors (RyRs), large-conductance Ca(2+)-activated K(+) (BK) channels, and small-conductance Ca(2+)-activated K(+) (SK) channels in the regulation of phasic contractions of guinea pig urinary bladder smooth muscle (UBSM). Nisoldipine (100 nM), a dihydropyridine inhibitor of VDCC, abolished spontaneous UBSM co...

Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced small-conductance Ca(2+)-activated K(+) (SK) current and increased excitability of presympathetic neurons in the paraventricular nucleus (PVN) in ANG II-salt HTN. Here, we hypothesized that ANG II-salt HTN would be accompanied by altered ...

Dopaminergic neurons in the ventral tegmental area (VTA) are important for the rewarding properties of drugs of abuse, including ethanol. We previously demonstrated that ethanol excites VTA neurons and that ethanol reduces the amplitude of the after hyperpolarization (AHP) that follows spontaneous action potentials. Because the small conductance calcium-activated potassium current (SK) is a com...

Aldosterone, which plays a key role in maintaining water and electrolyte balance, is produced by zona glomerulosa cells of the adrenal cortex. Autonomous overproduction of aldosterone from zona glomerulosa cells causes primary hyperaldosteronism. Recent clinical studies have highlighted the pathological role of the KCNJ5 potassium channel in primary hyperaldosteronism. Our objective was to dete...

We elucidated the interaction of small-conductance Ca(2+)-activated K(+) (SK(Ca)) channels and L-type Ca(2+) channels in muscarinic receptor-mediated control of catecholamine secretion in the isolated perfused rat adrenal gland. The muscarinic agonist methacholine (10-300 microM) produced concentration-dependent increases in adrenal output of epinephrine and norepinephrine. The SK(Ca) channel b...

Olivocochlear (OC) efferent suppression of auditory-nerve responses comprises a fast effect lasting tens of milliseconds and a slow effect building and decaying over tens of seconds. Both fast and slow effects are mediated by activation of the same alpha 9 nicotinic receptor. We have hypothesized that fast effects are generated at the OC synapse, but that slow effects reflect activation of calc...

There is now considerable evidence for the involvement of K+ channels in nitric oxide (NO) induced relaxation of smooth muscles including the myometrium. In order to assess whether apamin-sensitive K+ channels play a role in NO - induced relaxation of the human uterus, we have studied the effect of specific blockers of these channels on the relaxation of myometrium from non-pregnant women. In v...

ACh-induced endothelium-dependent relaxation in rabbit small mesenteric arteries is resistant to N-nitro-L-arginine (L-NA) and indomethacin but sensitive to high K+, indicating the relaxations are mediated by endothelium-derived hyperpolarizing factors (EDHFs). The identity of the EDHFs in this vascular bed remains undefined. Small mesenteric arteries pretreated with L-NA and indomethacin were ...

Fear extinction correlates with increased infralimbic (IL) neuronal excitability. Since small conductance Ca(2+)-dependent K(+) (SK) channels modulate neuronal excitability and certain types of learning and memory, pharmacological modulation of SK channels could be used to regulate IL excitability and fear extinction. To test this, we first determined the effect of blocking SK channels with apa...