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

(1) The effect of arginine-specific reagents on the sodium current (INa), potassium current (IK) and gating current (Igat) 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 INa without significantly altering its time course. After 30 min INa was reduced to 52% (pH 9.0) or 66% (pH 6.75-7.6) of the control value. IK was decreased to a similar extent without changing its kinetics. Igat was less affected than the ionic currents. (3) Externally applied phenylglyoxal markedly reduced INa and Igat, but many fibres were lost during or shortly after the treatment. A few min treatment with 5 mM phenylglyoxal at pH 9 reduced INa to 20% and the on-response of Igat to 69.5%. The effect was to a large extent irreversible. (4) External nitrophenylglyoxal and hydroxyphenylglyoxal significantly reduced INa and were less damaging than phenylglyoxal. INa 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 Igat to 62.5% of the control value, i.e. much less than INa. (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 INa(E) curve. (6) 20-30 mM glyoxal, 20 mM 1,2-cyclohexanedione and 10 mM 4-hydroxy-3-nitrophenylglyoxal had no effect on INa. (7) The results are compatible with the idea that arginine residues are principal components of the sodium channel macromolecule.