Suppression of calcium current by an endogenous neuropeptide in neurones of Aplysia californica.

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1. Actions of the neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2) and its derivative YGG-FMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2) on Ca2+ current were examined in identified, voltage-clamped neurones in the abdominal ganglion of Aplysia californica. 2. 'Puffed' application of either peptide at concentrations of 1-50 microM was followed by a transient partial suppression of pharmacologically isolated inward Ca2+ current elicited by a depolarizing step. At 20 degrees C, suppression was maximal 10-25 s following the brief puff of peptide, and lasted up to 90 s. Bath application of peptide had a steady suppressing effect, showing little if any desensitization. 3. Alternative sources of inward current suppression were ruled out, indicating that application of FMRFamide or YGG-FMRFamide produces a true decrease in Ca2+ current, rather than enhancement of possible contaminating outward (K+, H+ or Cl-) currents. 4. FMRFamide and YGG-FMRFamide were equally effective in suppressing Ca2+ current (apparent dissociation constant, KD* approximately 10 microM). However, only 30-50% of the total Ca2+ current elicited by voltage steps to above +10 mV appeared to be susceptible to suppression by even saturating concentrations of peptide. This, as well as a reduced effect of the peptides on Ca2+ current which was observed at potentials below +10 mV, may perhaps result from the presence of more than one class of Ca2+ channels, only one of which is sensitive to FMRFamide. 5. FMRFamide eliminated a constant fraction of Ca2+ current at all potentials above +10 mV, and had no direct effect on activation or inactivation of the remaining current. This behaviour is consistent with reduction in the number of functional Ca2+ channels by the peptide. 6. Suppression of Ca2+ current produced a concomitant depression of Ca2+-dependent K+ current, which was shown previously to be insensitive to FMRFamide when activated by direct ionophoretic injection of Ca2+ into the cell. 7. The effect of FMRFamide on Ca2+ current was normal following interference with or activation of known second-messenger systems, those involving adenosine 3',5'-cyclic monophosphate (cyclic AMP), cyclic GMP, Ca2+, inositol trisphosphate and protein kinase C. 8. Suppression of Ca2+ current by FMRFamide appeared to be mediated by the same receptor as enhancement by the peptide of K+ current resembling IK(S) (K+ current suppressed by serotonin), an effect seen in most of the same cells. Both effects of FMRFamide were mimicked by injection of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) into the cell, suggesting that the peptide may exert its effects by activating a guanosine 5'-triphosphate (GTP)-binding protein

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