FMRFamide modulates potassium currents in circadian pacemaker neurons of Bulla gouldiana.
The peptide FMRFamide (Phe-Met-Arg-Phe-NH(2)) is known to modulate the circadian pacemaker found in the eye of the marine snail Bulla gouldiana. In the present study, we investigated the cellular mechanisms underlying this modulation by examining the effects of FMRFamide on the membrane properties of the circadian pacemaker cells, known as basal retinal neurons in this preparation. Bath application of FMRFamide (0.1-1 microM) increased the membrane conductance, and hyperpolarized the membrane potential of these neurons. Next, perforated-patch recordings were used to demonstrate that FMRFamide reversibly increased the outward current amplitude due to an augmentation of a non-inactivating calcium-independent current. Reversal potential of the tail currents and its dependence on extracellular potassium concentration suggested potassium ions as the charge carrier for this current. The peptide-modulated outward current was blocked by 54% after bath application of the potassium channel blocker tetraethylammonium chloride and completely blocked by substituting cesium for intracellular potassium. Voltage dependence, activation kinetics and tail current kinetics of the FMRFamide-modulated current were consistent with values found for the delayed rectifier current.Overall, our data suggest that FMRFamide modulates a delayed rectifier potassium current and at least one other, less voltage-dependent conductance. This provides a mechanistic explanation for FMRFamide's ability to both shift the phase and attenuate light-induced phase shifts of the circadian pacemaker in B. gouldiana.
Michel
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Institut für Zoologie, Universität Leipzig, Talstrasse 33, D-04103 Leipzig, Germany. smichel@mednet.ucla.edu
Ehnert
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Schildberger
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K
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019835:FMRFamide / Q000378:metabolism* / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012908:Snails / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D005456:Fluorescent Dyes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019835:FMRFamide; D002118:Calcium; D016257:Fura-2