The potassium conductance of the resting squid axon and its blockage by clinical concentrations of general anaesthetics (original) (raw)
Related papers
The Journal of General Physiology, 1969
Giant axons were voltage-clamped in solutions of constant sodium concentration (230 mM) and variable potassium concentrations (from 0 to 210 mM). The values of the peak initial transient current, I(p), were measured as a function of conditioning prepulse duration over the range from less than 1 msec to over 3 min. Prepulse amplitudes were varied from E(m) = -20 mv to E(m) = -160 mv. The attenuation of the I(p) values in high [K(o)] was found to vary as a function of time when long duration conditioning potentials were applied. In both high and low [K(o)], I(p) values which had reached a quasi-steady-state level within a few milliseconds following a few milliseconds of hyperpolarization were found to increase following longer hyperpolarization. A second plateau was reached with a time constant of about 100-500 msec and a third with a time constant in the range of 30 to 200 sec. The intermediate quasi-steady-state level was absent in K-free ASW solutions. Sodium inactivation curves, normalized to I(pmax) values obtained at either the first or second plateaus, were significantly different in different [K(o)]. The inactivation curves, however, tended to superpose after about 1 min of hyperpolarizing conditioning. The time courses and magnitudes of the intermediate and very slow sodium conductance restorations induced by long hyperpolarizing pulses are in agreement with those predicted from the calculated rates and magnitudes of [K(+)] depletion in the space between the axolemma and the Schwann layer.
Local anesthetic block of sodium channels in normal and pronase-treated squid giant axons
Biophysical Journal, 1978
The inhibition of sodium currents by local anesthetics and other blocking compounds was studied in perfused, voltage-clamped segments of squid giant axon. When applied internally, each of the eight compounds studied results in accumulating "use-dependent" block of sodium currents upon repetitive pulsing. Recovery from block occurs over a time scale of many seconds. In axons treated with pronase to completely eliminate sodium inactivation, six of the compounds induce a time-and voltage-dependent decline of sodium currents after activation during a maintained depolarization. Four of the time-dependent blocking compounds-procaine, 9aminoacridine, N-methylstrychnine, and QX572-also induce altered sodium tail currents by hindering closure of the activation gating mechanism. Treatment of the axon with pronase abolishes use-dependent block completely by QX222, QX314, 9-aminoacridine, and N-methylstrychnine, but only partially by tetracaine and etidocaine. Two pulse experiments reveal that recovery from block by 9-aminoacridine or N-methylstrychnine is greatly accelerated after pronase treatment. Pronase treatment abolishes both use-dependent and voltage-dependent block by QX222 and QX314. These results provide support for a direct role of the inactivation gating mechanism in producing the long-lasting use-dependent inhibition brought about by local anesthetic compounds.
Effects of general anaesthetics on neuronal sodium and potassium channels
General pharmacology, 1992
1. The effects of clinical inhalation anaesthetics, such as halothane and methoxyflurane, and "model" anaesthetics, such as hydrocarbons and n-alkanols, on neuronal sodium and potassium channels are reviewed. 2. Lipid-based mechanisms for the actions of anaesthetics on the gating parameters of squid axon sodium and delayed rectifier potassium currents are considered in conjunction with evidence of more specific effects in other preparations, notably a fast inactivating potassium current in Helix neurones and a voltage-gated sodium current in rat dorsal root ganglion neurones. 3. The proconvulsant actions of some inhalation anaesthetics are discussed in relation to the induction of spontaneous firing of action potentials in the squid giant axon.
The Journal of General Physiology, 1969
Isolated giant axons were voltage-clamped in seawater solutions having constant sodium concentrations of 230 mM and variable potassium concentrations of from zero to 210 mM. The inactivation of the initial transient membrane current normally carried by Na+ was studied by measuring the Hodgkin-Huxley h parameter as a function of time. It was found that h reaches a steady-state value within 30 msec in all solutions. The values of h∞, τh, αh,and ßh as functions of membrane potential were determined for various [Ko]. The steady-state values of the h parameter were found to be inversely related, while the time constant, τh, was directly related to external K+ concentration. While the absolute magnitude as well as the slopes of the h∞ vs. membrane potential curves were altered by varying external K+, only the magnitude and not the shape of the corresponding τh curves was altered. Values of the two rate constants, αh and ßh, were calculated from h∞ and τh values. αh is inversely related to...
Effects of N-alcohols on potassium conductance in squid giant axons
European Biophysics Journal, 1987
The effect of bath application of several short chain N-alcohols on voltage-dependent potassium conductance has been studied in intact giant axons of Loligo forbesi under voltage-clamp conditions. All tested alcohols (methanol, ethanol, propanol, butanol, heptanol and octanol) were found to depress potassium conductance only at concentrations much larger than those necessary to reduce sodium conductance. The efficacy of the different molecules was correlated with the carbon-chain length. In all cases the effects were found to be at least partly reversible. Low concentrations of propanol (100 mM) or heptanol (1 mM) were found to increase potassium conductance whereas higher concentrations had the usual depressing effect. The two alcohols were found to induce a slow inactivation of the potassium conductance. A detailed analysis of the time course of the turning-on of the potassium current for various pulse potentials in the presence of TTX revealed that, for membrane potential values more positive than -20 mV, the time constant of activation was reduced in the presence of propanol or heptanol. The delay which separates the change in potential and the turning-on of the potassium current, which was systematically analysed for different pulse and prepulse potential values, was increased by the two alcohols, the curve relating this delay to prepulse potential being shifted towards larger (positive) delays. This high degree of complexity in the effects on potassium conductance suggests that the alcohol molecules modify several more or less independent mechanisms associated with the turning-on of the potassium current.
British Journal of Pharmacology, 2002
1 Combining the patch-clamp recordings in slice preparation with the`entire soma isolation' method we studied action of several local anaesthetics on delayed-recti®er K + currents in spinal dorsal horn neurones. 2 Bupivacaine, lidocaine and mepivacaine at low concentrations (1 ± 100 mM) enhanced delayed-recti®er K + current in intact neurones within the spinal cord slice, while exhibiting a partial blocking eect at higher concentrations (4100 mM). In isolated somata 0.1 ± 10 mM bupivacaine enhanced delayed-recti®er K + current by shifting its steady-state activation characteristic and the voltagedependence of the activation time constant to more negative potentials by 10 ± 20 mV.
Biophysical Journal, 1979
Quaternary strychnine blocks sodium channels from the axoplasmic side, probably by insertion into the inner channel mouth. Block is strongly voltage dependent, being more pronounced in depolarized than in resting axons. Using potential steps as a means to modulate the level of block, we investigate strychnine effects on sodium and gating currents at + 50 and-70 mV. We analyze our data in terms of the simplest possible model, wherein only an open channel may receive and retain a strychnine molecule. Our main findings are (a) block by strychnine and inactivation resemble each other and (b) block of sodium and gating currents by strychnine happen with closely similar time-courses. Our data support the hypothesis of Armstrong and Bezanilla (1977) wherein an endogenous blocking particle causes inactivation by inserting itself into the inner mouth of the sodium channel. Quaternary strychnine may act as an artificial substitute for the hypothetical endogenous blocking particle. Further, we suggest that at least 90% of the rapid asymmetrical displacement current in squid axons is sodium channel gating current, inasmuch as quaternary strychnine can block 90% of the displacement current simultaneously with sodium current. 'Cahalan, M. D., and W. Almers. 1979. Aftereffects of depolarization in squid giant axons poisoned with quaternary strychnine.
Modulation of aminopyridine block of potassium currents in squid axon
Biophysical Journal, 1986
Aminopyridines are known to block potassium (K) currents in excitable membranes in a manner dependent upon membrane potential, such that the block is relieved by depolarization and restored upon repolarization. In the present study, the effects of aminopyridines on voltage-dependent potassium (K) channels were examiped in internally perfused, voltage-clamped squid giant axons. The time course of block restoration after conditioning depolarization was found to be modulated by membrane electric field, K-channel gating, and external cations. Depolarized holding potentials accelerated block restoration without altering steady-state block levels, suggesting that the voltage dependence of block restoration may be related to K channel gating rather than drug binding per se. In support of this notion, low external calcium concentration, which shifts the voltage dependence of K-channel gating to more negative potentials, also accelerated block restoration. Conversely, the relationship between the rate of block restoration and membrane holding potential was shifted in the depolarizing direction by phloretin, an agent that shifts the dependence of K-channel opening on membrane potential in a similar manner. Modification of K-channel gating also was found to alter the rate of block restoration. Addition of internal zinc or internal treatment with glutaraldehyde slowed the time course of both K-channel activation and aminopyridine block restoration. Aminopyridines also were found to interact in the K channel with external Cs', NH4+, and Rb+, each of which slowed aminopyridine block restoration. Our results suggest that aminopyridines enter and occlude K channels, and that the availability of the binding site may be modulated by channel gating such that access is limited by the probability of the channel reaching an intermediate closed state at the resting potential.
Potassium conductance of the squid giant axon is modulated by ATP
1986
This communication reports a modulating effect of intracellular ATP on the steady-state and kinetic properties of the delayed rectifier of the giant axon of the squid. When internally dialyzed or perfused giant axons from Loligo pleiorLoigopealeiare voltage clamped at-60 mV and washed free of ATP, the potassium current at 0 mV is decreased, and