title: Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons.
abstract: We studied principal neurons from canine intracardiac (IC) ganglia to determine whether large-conductance calcium-activated potassium (BK) channels play a role in their excitability. We performed whole cell recordings in voltage- and current-clamp modes to measure ion currents and changes in membrane potential from isolated canine IC neurons. Whole cell currents from these neurons showed fast- and slow-activated outward components. Both current components decreased in the absence of calcium and following 1-2 mM tetraethylammonium (TEA) or paxilline. These results suggest that BK channels underlie these current components. Single-channel analysis showed that BK channels from IC neurons do not inactivate in a time-dependent manner, suggesting that the dynamic of the decay of the fast current component is akin to that of intracellular calcium. Immunohistochemical studies showed that BK channels and type 2 ryanodine receptors are coexpressed in IC principal neurons. We tested whether BK current activation in these neurons occurred via a calcium-induced calcium release mechanism. We found that the outward currents of these neurons were not affected by the calcium depletion of intracellular stores with 10 mM caffeine and 10 μM cyclopiazonic acid. Thus, in canine intracardiac neurons, BK currents are directly activated by calcium influx. Membrane potential changes elicited by long (400 ms) current injections showed a tonic firing response that was decreased by TEA or paxilline. These data strongly suggest that the BK current present in canine intracardiac neurons regulates action potential activity and could increase these neurons excitability.
authors.affiliation: Masonic Medical Research Laboratory, Utica, NY, USA.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Pérez
authors.forename: Mayurika
authors.initials: M
authors.lastname: Desai
authors.forename: Seth
authors.initials: S
authors.lastname: Anderson
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Scornik
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D019837:Ryanodine Receptor Calcium Release Channel; C048220:paxilline; D019789:Tetraethylammonium; D011188:Potassium; D002118:Calcium