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 (ER) near -70 mV, but with time, ER shifts toward a final value near 0 mV. This shift in ER is accompanied by a marked increase in conductance (slope of I/V relationship). Evidence is presented that the depolarizing shift in ER 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 ER following replacement of intracellular potassium with either cesium or tetraethylammonium. Since these results occur in calcium-free external media, the depolarizing shifts in ER and increased 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.