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 (IKF), which has very slow activation and deactivation kinetics. Addition of physiologically measured amounts of IKF to the model two-cell oscillator can account for the acceleratory effect of FMRFamide.