Modulation of a delayed-rectifier K+ current by angiotensin II in rat sympathetic neurons.
It is well known that angiotensin II (Angio II) mimics most of the muscarinic-mediated excitatory actions of acetylcholine on superior cervical ganglion neurons. For instance, in addition to depolarization and stimulation of norepinephrine release, muscarinic agonists and Angio II modulate the M-type K(+) current and the N-type Ca(2+) current. We recently found that muscarinic receptors modulate the delayed rectifier current I(KV) as well. Therefore a whole cell patch-clamp experiment was carried out in rat cultured sympathetic neurons to assess whether Angio II modulates I(KV). We found that Angio II increased I(KV) by about 30% with a time constant of approximately 30 s. In comparison, inhibition of M-current was faster (tau approximately 8 s) and stronger ( approximately 61%). Modulation of I(KV) was disrupted by the AT(1) receptor-antagonist losartan but not by the AT(2)-antagonist PD123319. I(KV) enhancement was reduced by the G-protein inhibitor GDP-beta-S, whereas current modulation remained unaltered after cell treatment with pertussis toxin. The peptidergic modulation of I(KV) was severely disrupted when internal ATP was replaced by its nonhydrolyzable analogue AMP-PNP. Angio II enhanced I(KV) and further reduced the stimulatory action of a muscarinic agonist on I(KV). Likewise, the muscarinc agonist enhanced I(KV) and occluded the effect of Angio II on I(KV). We have also found that the protein kinase C activator PMA enhanced I(KV), thereby mimicking and further attenuating the action of Angio II on I(KV). These results suggest that AT(1) receptors by coupling to pertussis toxin-insensitive G proteins, stimulate an ATP-dependent and PKC-mediated pathway to modulate I(KV).
Acosta
Eduardo
E
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av 25 de Julio 965, Col Villas San Sebastián, Colima, Colima, Mexico.
Mendoza
Víctor
V
Castro
Elena
E
Cruzblanca
Humberto
H
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017783:Superior Cervical Ganglion / Q000166:cytology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D051668:Delayed Rectifier Potassium Channels; D013873:Thionucleotides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D006153:Guanosine Diphosphate; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019808:Losartan; D013755:Tetradecanoylphorbol Acetate