The sodium channel and intracellular H⁺ blockage in squid axons

Abstract

Sodium channels in plasma membranes can be blocked by a large variety of toxins¹ and local anaesthetics². This property, however, is not confined to relatively large molecules. For instance, extracellularly applied small ions like hydrogen may also prevent the passive transport of permeant cations across open Na⁺ channels^3–6. A typical feature of this phenomenon^3,5 is that the blocking action of hydrogen is gradually relieved by increasing the voltage applied across the membrane. Although in the frog skeletal muscle there is no clear evidence for a similar intracellular action⁷, we report here for the squid giant axon remarkable effects on the ionic permeability of Na⁺ channels when the internal perfusate contains an excess of protons. Analysing the action of low pH inside and outside the fibre in terms of a kinetic model³, we could conclude that Na⁺ channels in squid axons are controlled by two independent groups: one with an apparent pK_a of 4.6 and the other with pK_a 5.8, the former feeling one-fifth of the applied membrane potential, the latter three-quarters. As with pharmacological agents⁸, we also show that the voltage-dependence of the H⁺ blockage is not affected by the presence of the inactivation gate.