Gallamine triethiodide‐induced modifications of sodium conductance in Myxicola giant axons.

Abstract

SUMMARY1. Internal gallamine triethiodide (Flaxedil) modifies Na+ channel kinetics in Myxicola axons but does not alter the K+ conductance. The drug has no effect externally.2. Gallamine initially increases the leakage conductance, but this effect completely reverses within 30 min despite the maintained presence of drug.3. Duringstep depolarizations to membrane potentials less than -10 mV, gallamine slows the rate of Na+ inactivation, but all channels which have opened can still inactivate. During depolarizations to more positive potentials, gallamine-modified Na+ currents show a biphasic decline, and at VM > -10 mV, Na+ inactivation is incomplete as evidenced by the large Na+ tail currents which follow pulses sufficiently long to have allowed complete inactivation of normal Na+ channels. The tail currents are slower than normal Na+ tails, and exhibit a pronounced hook. With gallamine, the fraction of Na+ channels which do not inactivate increases sigmoidally over the range 0 mV to + 80 mV.4. For VM > ENa, gallamine almost completely blocks outward Na+ currents. The block is determined by the direction of Na+ current, rather than the absolute membrane potential.5. Gallamine has no effect upon the rate of Na+ channel activation, the maximum Na+ conductance, the steady-state Na+ inactivation curve, or the rate ofdevelopment or removal of inactivation by prepulses.6. Gallamine eliminates physiological immobilization of intramembrane charge movements (QOFF and QON) and does not itself induce immobilization. Thus, in the presence of gallamine, QOFF following long pulses is the same as QOFF following short pulses.

High intracellular pH reversibly prevents gating-charge immobilization in squid axons

“…Our present data fit reasonably well with the model proposed by Armstrong and Bezanilla (5). These authors identify Na inactivation with an "endogenous blocking particle" located near the inner mouth of the channel that is positively charged when fully functioning (8,18), and supposed to possess a titratable side group with a pKa of 10.4. (7, 8).…”

“…However, the reverse is not necessarily true. For instance, in Myxicola axons internal application of gallamine enhances the FAST OFF response without affecting Na inactivation (18).…”

The Interaction of Nicotinic Receptor Antagonists at Muscarinic Receptors

“…Gallamine also inhibits sodium channels in frog muscle (Coloquhoun & Sheridan 1981) and when applied intracellularly can modify sodium channel inactivation in Myxicola giant axons (Schauf & Smith 1982). Whether such channel blocking actions can contribute to their antimuscarinic activity is not known, but it should be borne in mind that atropine, the classical muscarinic receptor antagonist, is also a potent inhibitor of potassium channel opening in the heart in the apparent absence of acetylcholine (Soejima & Noma 1984).…”