Mechanosensitive gating of atrial ATP-sensitive potassium channels.
Cell-attached and inside-out excised-patch recording techniques were used to search for mechanosensitive ion channels in neonatal and adult rat atrial myocytes. A channel activated by negative pressure applied to the patch, with a single-channel conductance of 52 pS in symmetric potassium solutions, was frequently observed. This channel has been identified as the atrial ATP-sensitive potassium (KATP) channel on the basis of its potassium selectivity, as well as its inhibition by ATP or tolbutamide in the inside-out excised patch. Mechanosensitive modulation of the KATP channel has not previously been reported. In the presence of 1 mM ATP, 10-50 microM pinacidil (a specific KATP channel agonist) does not significantly increase basal KATP channel activity; however, these concentrations of pinacidil potentiated the mechanosensitive modulation of the KATP channel. A hypotonic swelling protocol (a mechanical stimulus) was used in an effort to determine whether mechanosensitive modulation of this channel can generate significant whole-cell currents. Under perforated-patch whole-cell recording conditions, superfusion of atrial myocytes with a 240 mosm/kg solution (control solution, 290 mosm/kg) stimulated whole-cell currents with a magnitude similar to those activated by 10 microM pinacidil. These results demonstrate that the gating of the atrial KATP channel is mechanosensitive and suggest that mechanosensitive modulation may be an additional and significant mechanism, modulating channel activity under both physiological and pathological conditions.
Van Wagoner
D R
DR
Department of Cardiovascular Biology, Cleveland Clinic Foundation, Ohio 44195-5069.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006325:Heart Atria; D015640:Ion Channel Gating; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005905:Glyburide