Angiotensin II increases excitability and inhibits a transient potassium current in vagal primary sensory neurons.
The octapeptide angiotensin II (ANG II) plays a pivotal role in the maintenance of blood pressure by activating ANG II receptors located in variety of cell types including neurons housed in the central nervous system (CNS) and in the peripheral nervous system (PNS). ANG II (100 nM) blocked spike frequency accommodation (SFA) recorded with whole-cell patch technique in acutely isolated nodose ganglion neurons (NGN) from adult rats. ANG II increased the frequency of action potentials (AP) produced by supramaximal 500 ms depolarizing currents recorded in both tonic (16 Hz vs. 58 Hz, control vs. ANG II perfusion respectively, n=9) and phasic (1Hz vs. 38 Hz, n=13) NGNs. ANG II produced no significant changes in: the resting membrane potential (-51 mV vs. -50 mV, n=65), AP overshoot (46 mV vs. 41 mV, n=25), AP undershoot (-65 mV vs. -61 mV, n=25), AP duration (1 ms vs. 1.2 ms, n=25), and AP threshold (-40 mV vs. -43 mV, n=19). CV-11974 (600 nM), a specific AT1 receptor antagonist, prevented ANG II-evoked changes SFA (n=10). ANG II (100 nM) had no significant effect on total outward potassium current (I(K)) but inhibited a fast activating and fast inactivating I(K) recorded in the presence of TEA. A kinetically similar I(K) was also inhibited by 4-AP (3mM). In phasic NGNs, 4-AP occluded the effects of 100 nM ANG II on SFA. Our results indicate that ANG II can block an A-type of I(K) and that this effect may underlie the ANG II-mediated change in SFA.
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
Thaís Helena
TH
Moreira
Jader Santos
JS
Cruz
Daniel
D
Weinreich
D000200:Action Potentials / Q000187:drug effects*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D008297:Male; D008564:Membrane Potentials; D009620:Nodose Ganglion / Q000166:cytology* / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*
D000804:Angiotensin II; D011188:Potassium