Aims: 

Purpose of the study was to test the hypothesis that intracellular chloride and mitochondrial promiscuous channels are involved in the apoptosis and cardioprotection.

Methods: 

We measured effects of the chloride blockers DIDS, NPPB and Phloretin on H₂O₂-induced cardiomyocyte apoptosis and single channel properties of chloride and high conductance promiscuous channels derived from rat heart lysosomal and mitochondrial membranes incorporated in bilayer lipid membrane (BLM). Promiscuity of the single mitochondrial channels was measured as a voltage change of a voltage-dependent switch from K⁺ to Cl^- selectivity and an opposite switch.

Results: 

The chloride channel blockers (100 mmol/l) inhibited the H₂O₂ induced cardiomyocytes apoptosis. They inhibited the chloride channels at concentrations of 10-50 mmol/l by decreasing the channel open probability and the open dwell time. They affected promiscuity of the mitochondrial high conductance channels, influencing the voltage-switch and the K⁺/Clchannel activity.

Conclusion: 

The obtained results did not contradict the tested hypothesis. We may assume that the intracellular and the promiscuous channels may be involved in apoptosis and cardioprotection, however a definite proof is still missing. The results may contribute to understand a possible involvement of intracellular chloride and promiscuous channels in apoptosis and cardioprotection.

The work was supported by APPV grant 51-027404