Sodium channel blocker and the action potential
A neurotoxic peptide is applied to an isolated sensory neuron. Voltage-clamp recordings show that, at the peak of a normal action potential, the inward current is carried almost entirely by Na+. After peptide application, the peak inward current falls by 70%, but the resting membrane potential remains at -70 mV and the outward K+ current is unchanged. The threshold potential is -55 mV. A student concludes that the peptide 'blocks all sodium channels, so no action potential can ever fire'. When the stimulus strength is doubled, a smaller, slower action potential is still recorded.
1. Evaluate the student's conclusion using the data.
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The conclusion is partly wrong. If all Na+ channels were blocked, no inward Na+ current could occur, so threshold could not be reached and no action potential would fire. The 70% reduction shows a partial block, consistent with a competitive or use-dependent blocker acting on a fraction of channels. With enough stimulus, the remaining 30% of channels can still open, so threshold can be reached, but recruitment is slower and less synchronous. That explains the smaller, slower action potential. Resting potential is unchanged because resting permeability is dominated by K+ leak channels, not Na+ channels. A better conclusion: the peptide reduces the number of available voltage-gated Na+ channels, raising the effective threshold and reducing action potential amplitude and conduction speed, but does not abolish excitability.
2. Predict the effect on conduction velocity and explain the mechanism.
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Conduction velocity should fall. Action potential propagation depends on local circuit currents depolarising the next patch of membrane to threshold. A smaller peak depolarisation produces weaker local currents, so each segment takes longer to reach -55 mV. Fewer available Na+ channels also mean the upstroke is slower (lower rate of depolarisation), which further slows propagation. If the axon were myelinated, the effect would be amplified at nodes of Ranvier because saltatory conduction relies on dense nodal Na+ channel clusters. The prediction is a reduced velocity, not a complete block, provided the stimulus is above the new effective threshold.