Block of the helix FMRFamide-gated Na+ channel by FMRFamide and its analogues.

1. In Helix neurones high doses of Phe-Met-Arg-Phe-NH2 (FMRFamide) often evoke biphasic inward whole-cell currents with brief application, and suppression of the current with prolonged application. With outside-out patches, a transient early suppression of the unitary current amplitude was seen following application of high doses of FMRFamide. 2. Continuous application of a concentration of FMRFamide from 30 microM to 1 mM resulted in a reduction in the amplitude of the unitary currents and an increase in open state noise. There was also an increase in the occurrence of smaller, 'subconductance' currents with the higher concentrations of FMRFamide. Similar effects were seen with FMRFamide on FaNaC expressed in oocytes. The FMRFamide analogues FLRFamide and WnLRFamide were more effective in evoking the lower conductance state. These effects of agonist at high concentrations were voltage dependent suggesting channel block. 3. A similar effect was seen when one of the related peptides FKRFamide, FM(D)RFamide, nLRFamide or N-AcFnLRFamide was co-applied with a low FMRFamide concentration. However, the non-amidated peptides FKRF, FLRF and nLRF and also WMDFamide did not have this effect. 4. The inhibition of unitary currents induced by amiloride was qualitatively different from that produced by FMRFamide analogues with no obvious occurrence of subconductance levels. FMRFamide-gated channels were also blocked by guanidinium, but only at very high concentrations. 5. The results strongly suggest a partial inhibition of current flow through the FMRFamide- gated channel by some part of the agonist or the related antagonist peptide molecules.