Kv2 channel regulation of action potential repolarization and firing patterns in superior cervical ganglion neurons and hippocampal CA1 pyramidal neurons.
Kv2 family "delayed-rectifier" potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60-80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from -70 mV, but not -80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at -70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation.
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Pin W
PW
Liu
Bruce P
BP
Bean
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D060829:Arthropod Proteins; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology*; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051669:Shab Potassium Channels / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D017783:Superior Cervical Ganglion / Q000166:cytology*
D060829:Arthropod Proteins; C550903:GxTX-1E, Plesiophrictus guangxiensis; D010455:Peptides; D026902:Potassium Channel Blockers; D051669:Shab Potassium Channels; D013111:Spider Venoms
Guangxitoxin; Hodgkin-Huxley kinetics; Kv2; activation; deactivation; delayed-rectifier potassium channel