A slow outward current activated by FMRFamide in heart interneurons of the medicinal leech

The endogenous neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH₂) can accelerate the oscillation of reciprocally inhibitory pairs of interneurons that pace heartbeat in the medicinal leech. A model based on all available biophysical data of a two-cell heart interneuron oscillator provides a theoretical basis for understanding this modulation. Previously observed modulation of K⁺ currents by FMRFamide cannot account for this acceleratory effect in the model. This observation prompted the present reexamination of K⁺ currents in heart interneurons. We devised better methods for separation of the various components of K⁺ current and more accurately measured their activation and deactivation kinetics. Moreover, we demonstrated that FMRFamide activates a previously undetected K⁺ current (I(KF)), which has very slow activation and deactivation kinetics. Addition of physiologically measured amounts of I(KF) to the model two-cell oscillator can account for the acceleratory effect of FMRFamide.