Decreases in Ca2+-dependent K+-currents due to cyclic guanosine monophosphate are not dependent on phosphorylation

Two-microelectrode voltage clamping experiments were performed on isolated snail neurons to measure the Ca2+-dependent. potential-dependent K+ current (I(C)), with assessment of the effects of penetrating cGMP analogs on this current - dibutyryl cGMP (dcGMP) and 8-Br-cGMP. Both of these penetrating cGMP analogs rapidly and reversibly decreased the amplitude of I(C). cGMP analogs produced no shifts in the volt-ampere characteristics of the efflux current along the voltage axis. dcGMP and 8-Br-cGMP had no effect on the influx Ca2+ current. The non-specific protein kinase inhibitor H-8 decreased or had no effect on I(C) in different cells. The effects of both dcGMP and 8-Br-cGMP persisted in the presence of H-8. Decreases in I(C) in the presence of cGMP analogs also persisted in the presence of the protein phosphatase inhibitor okadaic acid. These results lead to the conclusion that decreased conductivity of Ca2+-dependent K+ channels occurring in response to cGMP is not associated with phosphorylation.