Figure 6.

cis-Oleamide is a specific state-dependent antagonist of the voltage-gated Na⁺ channel. (A) Spikes evoked by current passage through the patch micro-electrode (at 1 Hz, averages of 50 consecutive sweeps) were not altered by 64 μM cOA but were fully blocked by 50 nM TTX. (b) Compounded data from seven replicated experiments on unitary action potentials. Bars represent mean+s.e.mean. (c) In contrast cOA (10–64 μM) markedly suppressed sustained repetitive firing (SRF) in salines containing Co²⁺ to suppress voltage-gated Ca²⁺ currents. (d) Block of SRF was concentration- and voltage-dependent (the blocking action could be partially reversed by hyperpolarization of the impaled cell, not shown). Each data point represents mean±s.e.mean for the indicated number of replicates. Note the very steep slope (Hill coefficient of approximately 3). (e) The high affinity block produced by cOA was not seen with high concentrations of hydrophobic congeners.