A Single or Dual Channel in Nerve Membranes

Dear Sir: In his recent letter to you, Dr. Mullins suggests that the evidence on squid axon membrane conductances said to be compatible with the notion of two independent ionic conductances for Na and K "is not at present compelling." We certainly agree with this and furthermore would point out that we do not yet see any experiment which could help us choose definitively between a single channel (of the Mullins' 1959 type) or a pair of independent channels. 1 Dr. Mullins makes an interesting proposal for a conclusive experimental demonstration of two channels in the membrane; this would be an observation in which both ionic conductances were simultaneously and fully "turned on," giving rise to a total membrane conductance of twice the normal maximum value for either ionic species. We agree that perhaps this would be sufficient to establish the two-channel notion as the preferred theory. Mullins declares that such data have not been found, nor do we know of any. However, it does not appear necessary to require that both channels be simultaneously open, although they "both could, in principle, be opened at the same time." It is quite possible that an observation may be made in which there is some increase (e.g., 10-20%) in the total membrane conductance. Before this is said to strongly lend weight to the two-channel notion, the single channel hypothesis should be carefully examined to see whether it allows such a situation. For example, in his original treatment, Mullins (1959) set up different dispersions about the Na and K pore sizes in order to match the available experimental data on conductance. It is, in principle, possible that an agent could reduce the dispersion about the potassium pore size and produce twice the normal potassium conductance. Then the question should be raised as to whether or not this narrower distribution would also have an associated minor peak 2 at a pore size compatible with Na flow. Although there is no single definitive experimental observation in hand, several 1 There is also a leakage component (Hodgkin and Huxley, 1952) in the membrane currents of squid axons. Myellnated nerve fibers might be said to have "multichanneled" membranes, because there are at least four components including the leakage (Frankenhaeuser and Huxley, 1964). 2 See Fig. 8 of Mullins (1959) where the sharp peak for Na was associated with a minor peak at a Rb pore size.