Control of ionic permeability by membrane charged groups: dependency on pH, depolarization, tetrodotoxin and procaine

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 (Ko = 5.4 mM, pH = 7), P(K) = 1.33 X 10-5, P(Cl) - 1.49 X 10-6, and P(Na) = 1.92 X 10-8 cm/s. Increasing external potassium results in a dramatic membrane conductance change around Ko = 12 mM (Vm = -60 mV) which results primarily from changes in P(Na) and P(Cl). In elevated potassium (Ko = 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 the four protein molecules interact to form the Na and Cl ionic channels. Tetrodotoxin has minimal effects on passive permeabilities but reduce 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 association and control over the different ion permeabilities. In addition, membrane conformational changes are also involved in permeability control.