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A slow outward current activated by FMRFamide in heart interneurons of the medicinal leech
1Department of Biology, Emory University, Atlanta, Georgia 30322, USA.
Abstract:
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.
Insights
The neuropeptide FMRFamide accelerates leech heart interneuron oscillations by activating a novel potassium current (IKF). This finding explains previously unexplained cardiac pacing modulation in leeches.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Biophysics
Background:
- The neuropeptide FMRFamide modulates heartbeat in leeches by affecting interneuron oscillations.
- Existing models could not explain FMRFamide's acceleratory effect on heart interneuron activity.
- Previous studies suggested FMRFamide modulated K+ currents, but this did not fully account for the observed effects.
Purpose of the Study:
- To re-examine potassium (K+) currents in leech heart interneurons.
- To identify the specific ionic mechanisms underlying FMRFamide-induced acceleration of heart interneuron oscillations.
- To refine computational models of cardiac pacing.
Main Methods:
- Improved techniques for separating and measuring components of K+ current.
- Detailed kinetic analysis of K+ current activation and deactivation.
- Incorporation of newly identified currents into a two-cell interneuron oscillator model.
Main Results:
- FMRFamide activates a previously undetected K+ current, termed IKF.
- IKF exhibits notably slow activation and deactivation kinetics.
- Modeling incorporating IKF quantitatively reproduced the acceleratory effect of FMRFamide on the oscillator.
Conclusions:
- A novel K+ current (IKF) is identified as the primary mediator of FMRFamide's effect on leech heart interneuron oscillations.
- The slow kinetics of IKF are crucial for explaining the observed acceleration of cardiac pacing.
- This discovery refines our understanding of neuropeptide modulation of neural circuits controlling vital functions.