Desensitization to ANG II in guinea pig ileum depends on membrane repolarization: role of maxi-K(+) channel.
Desensitization of ANG II tonic contractile response of the guinea pig ileum is related to membrane repolarization determined by Ca(2+)-activated K(+) (maxi-K(+)) channel opening. ANG II-stimulated depolarized myocytes presented sustained activation of maxi-K(+) channels, characterized by reduction from 415 to 12 ms of the closed time constant. ANG II desensitization was prevented by 100 nM iberiotoxin, being reversible within 30 min. Depolarization by KCl, higher than 4 mM, impaired desensitization, suggesting that the membrane potential must attain a threshold to counteract the repolarization induced by maxi-K(+) channel opening. Once this value is attained, there is no time dependency because the desensitization process was shut off by addition of KCl along the time course of the tonic response. In contrast, the sustained ACh tonic component was not altered by these maneuvers. We conclude that desensitization of the ANG II tonic component is foremost due to the opening of maxi-K(+) channels, leading to membrane repolarization, thus closing the voltage-dependent Ca(2+) channels responsible for the Ca(2+) influx that sustains the tonic component in this muscle.
Silva
B A
BA
Department of Biophysics, Universidade Federal de São Paulo, Escola Paulista de Medicina, 04023-062 São Paulo, Brazil.
Nouailhetas
V L
VL
Aboulafia
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008566:Membranes / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D000804:Angiotensin II; D000109:Acetylcholine