Properties of cardiac I_leak induced by photosensitizer-generated reactive oxygen

We reported previously that photomodification of single frog cardiac cells by Rose Bengal induces a time-independent current, designated I_leak, having a linear current-voltage (I/V) relationship. The purpose of the present study is to better characterize the properties of I_leak. Initially, I_leak has a reversal potential (E_R) near -70 mV, but with time, E_R shifts toward a final value near 0 mV. This shift in E_R is accompanied by a marked increase in conductance (slope of I/V relationship). Evidence is presented that the depolarizing shift in E_R with time during photomodification results from a loss of membrane selectivity allowing sodium to make an increasing contribution to I_leak. Potassium also contributes to I_leak, as indicated by marked depolarizing shifts in E_R following replacement of intracellular potassium with either cesium or tetraethylammonium. Since these results occur in calcium-free external media, the depolarizing shifts in E_R and conductance are not related to activation of a calcium-dependent nonselective cation channel. However, I_leak does have some properties similar to nonselective cation currents recently reported to be activated by membrane breakdown products such as arachidonic acid and lysophosphoglycerides.