Modulation of excitability by alpha-dendrotoxin-sensitive potassium channels in neocortical pyramidal neurons.
Many neurons transduce synaptic inputs into action potentials (APs) according to rules that reflect their intrinsic membrane properties. Voltage-gated potassium channels, being numerous and diverse constituents of neuronal membrane, are important participants in neuronal excitability and thus in synaptic integration. Here we address the role of dendrotoxin-sensitive "D-type" potassium channels in the excitability of large pyramidal neurons in layer 5 of the rat neocortex. Low concentrations of 4-aminopyridine or alpha-dendrotoxin (alpha-DTX) dramatically increased excitability: the firing threshold for action potentials was hyperpolarized by 4-8 mV, and the firing frequency during a 1-sec-long 500 pA somatic current step was doubled. In nucleated outside-out patches pulled from the soma, alpha-DTX reversibly blocked a slowly inactivating potassium current that comprised approximately 6% of the total. This current first turned on at voltages just hyperpolarized to the threshold for spiking and activated steeply with depolarization. By assaying alpha-DTX-sensitive current in outside-out patches pulled from the axon and primary apical dendrite, it was found that this current was concentrated near the soma. We conclude that alpha-DTX-sensitive channels are present on large layer 5 pyramidal neurons at relatively low density, but their strategic location close to the site of action potential initiation in the axon may ensure that they have a disproportionate effect on neuronal excitability. Modulation of this class of channel would generate a powerful upregulation or downregulation of neuronal output after the integration of synaptic inputs.
Bekkers
J M
JM
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia. John.Bekkers@anu.edu.au
Delaney
A J
AJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology*; D066298:In Vitro Techniques; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000145:classification / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology
D004546:Elapid Venoms; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; C020273:dendrotoxin; D015761:4-Aminopyridine; D011188:Potassium