Pressure dependence of sodium gating currents in the squid giant axon

Abstract

Asymmetric displacement currents, Ig, were measured in squid axons at different hydrostatic pressures, P, up to 60 MPa. Potassium and sodium currents were abolished by intracellular Cs+ and TEA+, by extracellular Tetrodotoxin (TTX), and by Na+ substitution with Tris+. The time course of Ig became progressively slower with increasing pressure, and the amplitude decreased. With appropriate scaling in time and amplitude, Ig records at any given P could be made to superimpose very well with those obtained at atmospheric pressure. The same scaling factors yielded a good superposition of all records obtained for voltage steps to membrane potentials in the range -30 to +42 mV. The ratio between the amplitude and time factors was larger than unity and increased with P, indicating a progressive decrease (up to 35% at 60 MPa) of the total charge displaced, Q, with no significant change in its voltage dependence. The time-scaling factor increased exponentially with P, as expected if all the steps involved in the opening of a sodium channel, and producing a major charge redistribution, have the same activation volume, delta V not equal to g approximately 17 cm3/mol. This value is roughly one-half of that characterizing the pressure dependence of sodium current activation, suggesting that some late, rate-limiting step in the opening of sodium channels has a large activation volume without being accompanied by an easily detected charge movement. Part of the decrease of Q with pressure could be attributed to an increase in sodium inactivation. However, we cannot exclude the possibility that there is a reversible reduction in the number of fast activating sodium channels, similar to the phenomenon that has been reported to occur at low temperatures (Matteson and Armstrong 1982).

Temperature dependence of gating current in myelinated nerve fibers

“…It is surprising that Qon(E) curves are shifted to the left, whereas PNa(E) curves are shifted to the right when temperature is increased. A similar observation has been reported by Conti et al (1982Conti et al ( , 1984, who found that increasing pressure shifts PNa(E) towards positive potentials, but does not shift Qon(E). The results of the present paper and the findings of Conti et al (1982Conti et al ( , 1984 can be explained with the hypothesis that transitions between the closed states of the Na channel contribute far more to the total charge movement than the final step preceding the opening of the Na channel.…”

Single acetylcholine receptor channel currents recorded at high hydrostatic pressures.

“…However, the apparent activation volumes describing the pressure dependencies of a* and 13* are expected to be weighted functions of several AVts and depend also on the relative probability of the various channel states. The effects described here, as well as those observed for ionic channels in nerves (5)(6)(7)(8)24) are readily appreciable only above 10 MPa. Therefore, they are unlikely to play a major role in the physiology ofthe high pressure nervous syndrome, which can develop in whole organisms at pressures as low as 6 MPa (3).…”

Gating of sodium and potassium channels

“…The last step, however, could be uncharged and not too fast because the sequence may have slower steps as it gets closer to the open state. Conti et al (1984) have determined the activation volume of the gating reaction by measuring gating currents and ionic currents at high hydrostatic pressures. They found that the activation volume determined from the gating current is less than the volume measured from the sodium current.…”