Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons.
Voltage-gated potassium channels, Kv1.1, Kv1.2 and Kv1.6, were identified as PCR products from mRNA prepared from nodose ganglia. Immunocytochemical studies demonstrated expression of the proteins in all neurons from ganglia of neonatal animals (postnatal days 0-3) and in 85-90 % of the neurons from older animals (postnatal days 21-60). In voltage clamp studies, alpha-dendrotoxin (alpha-DTX), a toxin with high specificity for these members of the Kv1 family, was used to examine their contribution to K(+) currents of the sensory neurons. alpha-DTX blocked current in both A- and C-type neurons. The current had characteristics of a delayed rectifier with activation positive to -50 mV and little inactivation during 250 ms pulses. In current-clamp experiments alpha-DTX, used to eliminate the current, had no effect on resting membrane potential and only small effects on the amplitude and duration of the action potential of A- and C-type neurons. However, there were prominent effects on excitability. alpha-DTX lowered the threshold for initiation of discharge in response to depolarizing current steps, reduced spike after-hyperpolarization and increased the frequency/pattern of discharge of A- and C-type neurons at membrane potentials above threshold. Model simulations were consistent with these experimental results and demonstrated how the other major K(+) currents function in response to the loss of the alpha-DTX-sensitive current to effect these changes in action potential wave shape and discharge.
Glazebrook
Patricia A
PA
Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44109, USA.
Ramirez
Angelina N
AN
Schild
John H
JH
Shieh
Char-Chang
CC
Doan
Thanh
T
Wible
Barbara A
BA
Kunze
Diana L
DL
D000465:Algorithms; D000818:Animals; D015153:Blotting, Western; D018076:DNA, Complementary / Q000187:drug effects / Q000502:physiology; D051668:Delayed Rectifier Potassium Channels; D004546:Elapid Venoms / Q000494:pharmacology; D004594:Electrophysiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051662:Kv1.1 Potassium Channel; D051663:Kv1.2 Potassium Channel; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D051668:Delayed Rectifier Potassium Channels; D004546:Elapid Venoms; C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; C020273:dendrotoxin