The KCNQ/M-current modulates arterial baroreceptor function at the sensory terminal in rats.
The ion channels responsible for the pattern and frequency of discharge in arterial baroreceptor terminals are, with few exceptions, unknown. In this study we examined the contribution of KCNQ potassium channels that underlie the M-current to the function of the arterial baroreceptors. Labelled aortic baroreceptor neurons, immunohistochemistry and an isolated aortic arch preparation were used to demonstrate the presence and function of KCNQ2, KCNQ3 and KCNQ5 channels in aortic baroreceptors. An activator (retigabine) and an inhibitor (XE991) of the M-current were used to establish a role for these channels in setting the resting membrane potential and in regulating the response to ramp increases in arterial pressure. Retigabine raised the threshold for activation of arterial baroreceptors and shifted the pressure-response curve to higher aortic pressures. XE991, on the other hand, produced an increase in excitability as shown by an increase in discharge at elevated pressures as compared to control. We propose that KCNQ2, KCNQ3 and KCNQ5 channels provide a hyperpolarizing influence to offset the previously described depolarizing influence of the HCN channels in baroreceptor neurons and their terminals.
Rammelkamp Center for Research and Education R326, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109-1998, USA.
Cynthia L
CL
Wladyka
Bin
B
Feng
Patricia A
PA
Glazebrook
John H
JH
Schild
Diana L
DL
Kunze
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D051658:KCNQ2 Potassium Channel / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010655:Phenylenediamines / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D000927:Anticonvulsants; D002219:Carbamates; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C496915:Kcnq2 protein, rat; C496918:Kcnq3 protein, rat; C501028:Kcnq5 protein, rat; D010655:Phenylenediamines; C101866:ezogabine