Selective potentiation of N-type calcium channels by angiotensin II in rat subfornical organ neurones.
1. Here we have characterized Ca(2+) currents in rat subfornical organ neurones, and their modulation by angiotensin II. Currents were of the high voltage-activated (HNA) subtype, as the threshold for activation was near -30 mV (mid-point potential (V(50)) of activation -14 mV). Using Ba(2+) as the charge carrier, little inactivation was observed, and it occurred only at depolarized potentials (V(50) of inactivation -12 mV). More inactivation was observed using Ca(2+) as the charge carrier, indicating that Ca(2+)-dependent inactivation plays a role in regulating Ca(2+) channel function in subfornical organ (SFO) neurones. 2. The net Ba(2+) current could be blocked by Cd(2+) (EC(50) 1.6 microM), confirming that currents are of the HVA variety. By using selective antagonists, we identified the presence of both L- and N-type channels; 20 microM nifedipine blocked 22 +/- 1 % of the current, while omega-conotoxin GVIA blocked 65 +/- 7 %, indicating that these currents make up the net current through Ca(2+) channels. 3. Angiotensin II potentiated the inward current throughout the range of activation. Using depolarizing voltage ramps, 1 nM angiotensin potentiated the peak current by 14 +/- 5 %. We then used selective blockade of the HVA component currents; 20 microM nifedipine failed to prevent the potentiation by angiotensin II (12 +/- 5 %), while blocking N-type channels with omega-conotoxin GVIA blocked the facilitation by ANG (2.3 +/- 2 %). Losartan (1 microM) prevented the actions of ANG on the inward current (1.6 +/- 1 %), indicating that the selective effects of ANG on N-type channels in SFO neurones are mediated by AT(1) receptors.
Washburn
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DL
Department of Physiology, Queen's University, Kingston, ON, Canada K7L 3N6.
Ferguson
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AV
D000465:Algorithms; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects; D013356:Subfornical Organ / Q000166:cytology* / Q000187:drug effects*
D002120:Calcium Channel Agonists; D020864:Calcium Channels, N-Type; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D001464:Barium