title: Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.
abstract: Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Hlubek
authors.forename: P
authors.initials: P
authors.lastname: Cobbett
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D019256:Cadmium Chloride