Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.
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.
Hlubek
M D
MD
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA.
Cobbett
P
P
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
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D019256:Cadmium Chloride