The action of arginine-specific reagents on ionic and gating currents in frog myelinated nerve

Abstract

(1) The effect of arginine-specific reagents on the sodium current ( I Na), potassium current ( I K) and gating current ( I gat) of myelinated nerve fibres was investigated. (2) Externally applied camphorquinone-10-sulfonic acid (Cqs-OH) had little effect, but 50 mM Cqs-OH applied to the cut ends of the fibre progressively reduced the amplitude of I Na without significantly altering its time course. After 30 min I Na was reduced to 52% (pH 9.0) or 66% (pH 6.75–7.6) of the control value. I K was decreased to a similar extent without changing its kinetics. I gat was less affected than the ionic currents. (3) Externally applied phenylglyoxal markedly reduced I Na and I gat, but many fibres were lost during or shortly after the treatment. A few min treatment with 5 mM phenylglyoxal at pH 9 reduced I Na to 20% and the on-response of I gat to 69.5%. The effect was to a large extent irreversible. (4) External nitrophenylglyoxal and hydroxyphenylglyoxal significantly reduced I Na and were less damaging than phenylglyoxal. I Na was decreased to 34.5% by 10 mM nitrophenylglyoxal and to 28.3% by 20 mM hydroxyphenylglyoxal. The effect of nitrophenylglyoxal was little reversible, but that of hydroxyphenylglyoxal to a large extent reversible. 20 mM hydroxyphenylglyoxal reduced the on-response of I gat to 62.5% of the control value, i.e. much less than I Na. (5) 5 mM phenylglyoxal, 10 mM nitrophenylglyoxal and 20 mM hydroxyphenylglyoxal shifted the steady-state inactivation curve by 10–15 mV to more negative values of membrane potential but did not affect the descending branch of the I Na( E) curve. (6) 20–30 mM glyoxal, 20 mM 1,2-cyclohexanedione and 10 m 4-hydroxy-3-nitrophenylglyoxal had no effect on I Na. (7) The results are compatible with the idea that arginine residues are principal components of the sodium channel macromolecule.