PLATELET-ACTIVATING-FACTOR ACTIVATES CARDIAC GK VIA ARACHIDONIC-ACID METABOLITES

Platelet-activating factor (PAF), added to the bathing solution, stimulated the cardiac muscarinic K+ channel (K(ACh)) in the cell-attached patch (no agonist in the pipette). The PAF-induced K(ACh) channel activation was blocked by WEB2086, a PAF-receptor inhibitor, indicating that the PAF-receptor mediated the response. PAF-induced activation was prevented by nordihydroguaieretic acid, a lipoxygenase inhibitor, and AA-861, a 5-lipoxygenase inhibitor, but was not affected by indomethacin, a cyclo-oxygenase inhibitor. The PAF-induced K(ACh) channel activity disappeared upon formation of inside-out patch. In this inside-out patch, intracellular GTP alone induced maximal channel reactivation, which was inhibited by GDP-beta-S. These results suggest that 5-lipoxygenase metabolites of PAF-released arachidonic acid cause a persistent stimulation of G(K) but not the K(ACh) channel itself, resulting in a receptor-independent activation of the K(ACh) channel by GTP.