Control of Ionic Permeability by Membrane Charged Groups: Dependency on pH, Depolarization, Tetrodotoxin and Procaine

Abstract

The membrane permeabilities of K, Na, and Cl were determined in crayfish giant axons from pH 3.8 to 11.4. In general, cation permeability increases with pH while anion permeability decreases. In normal saline (K = 5.4 mM, pH = 7), P_K = 1.33 × 10⁻⁵, P_C1 = 1.49 × 10⁻⁶, and P_Na = 1.92 × 10⁻⁸ cm/s. Increasing external potassium results in a dramatic membrane conductance change around K_o = 12 mM (V_m = −60 mV) which results primarily from changes in P_Na and P_Cl. In elevated potassium (K_o = 40 mM, pH = 7), P_K P_Cl, and P_Na increase by 1.45, 8.1, and 14.2. In the potassium depolarized axon, P_Na and P_Cl show a cooperative change when pH is altered through the imidazole pK region (pK = 6.3). These changes are not seen in normal saline, or with P_K. A Hill coefficient n = 4 was found for the cooperative change of P_Na and P_Cl. An interpretation here is that four protein molecules interact to form the Na and Cl ionic channels. Tetrodotoxin has minimal effects on passive permeabilities but reduces the Hill coefficient n for P_Na but not P_Cl, while procaine reduces n for both P_Na and P_Cl. The results show that membrane fixed charged groups have varied associations and control over the different ion permeabilities. In addition, membrane conformational changes are also involved in permeability control.