MECHANOSENSITIVE GATING OF ATRIAL ATP-SENSITIVE POTASSIUM CHANNELS

Cell-attached and inside-out excised-patch recording techniques were u sed 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 id entified as the atrial ATP-sensitive potassium (K(ATP)) channel on the basis of its potassium selectivity, as well as its inhibition by ATP or tolbutamide in the inside-out excised patch. Mechanosensitive modul ation of the K(ATP) channel has not previously been reported. In the p resence of 1 mM ATP, 10-50 muM pinacidil (a specific K(ATP) channel ag onist) does not significantly increase basal K(ATP) channel activity; however, these concentrations of pinacidil potentiated the mechanosens itive modulation of the K(ATP) channel. A hypotonic swelling protocol (a mechanical stimulus) was used in an effort to determine whether mec hanosensitive modulation of this channel can generate significant whol e-cell currents. Under perforated-patch whole-cell recording condition s, superfusion of atrial myocytes with a 240 mosm/kg solution (control solution, 290 mosm/kg) stimulated whole-cell currents with a magnitud e similar to those activated by 10 muM pinacidil. These results demons trate that the gating of the atrial K(ATP) channel is mechanosensitive and suggest that mechanosensitive modulation may be an additional and significant mechanism, modulating channel activity under both physiol ogical and pathological conditions.