A new non-voltage-dependent, epithelial-like Na+ channel in vascular smooth muscle cells.
A new type of Na+ channel was identified in smooth muscle cells of the rat aortic cell line A7r5, and in smooth muscle cells cultured from rat aorta and rat portal vein. The channel is highly selective for Na+ (PNa/PK greater than 11). It is active in cell-attached patches, and independent of the trans-patch membrane potential. The single channel conductance is low (10.7 pS). Two substates were identified. This channel is insensitive to effectors of other types of Na+ channels, such as amiloride (100 microM) or tetrodotoxin (100 microM). It is inhibited by phenamil at high concentrations (greater than 10 microM). The mean open state probability P(O) varied from patch to patch (0.05-0.88). Kinetics analysis reveals a complex behaviour: open times separate in short (tau 1 = 84 ms) and long (tau 2 = 845 ms) openings and closed times separate into short (tau 1 = 60 ms) and long closures (tau 2 = 272-3130 ms). Short openings and long closures are preponderant at a low P(O). Long openings are absent in the presence of phenamil (50 microM) and are unaffected by amiloride (100 microM). Fluctuations of the channel activity in cell-attached patches and the fast disappearance after excision suggest that this channel is under metabolic control. This vascular smooth muscle channel appears to be a potentially important Na+ entry pathway for vascular cells and an amiloride-resistant homologue of the epithelial Na+ channel.
Van Renterghem
C
C
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Lazdunski
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M
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D004848:Epithelium / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011169:Portal Vein / Q000166:cytology / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D015222:Sodium Channels; C047088:phenylamil; D000584:Amiloride