Effects of a synthetic cationic polymer on sodium and potassium currents of frog nerve fibres.
(1) Voltage-clamped nerve fibres of the frog Rana esculenta were treated with the synthetic cationic polymer hexadimethrine bromide (HDM) [Polybrene]. (2) 1 microM HDM irreversibly reduced INa to about 65% of its original size. The time to peak remained almost unaffected, while the decaying phase of the currents (for pulse potentials less than -10 mV) became accelerated. The size of INa was hardly reduced further even with a 1,000-fold higher concentration of HDM. (3) The cationic polymer HDM was without effect on the voltage-dependence of activation and there was only a small shift (-4.5 mV) of the voltage dependence of steady-state inactivation. (4) Variation of [Ca2+] in the Ringer solution shifted the voltage-dependence of activation and of steady-state inactivation to the same extent before and after treatment with HDM. By contrast, 0.5 mM La3+ markedly decreased the Ca2+-induced shifts. (5) The decrease of the size of INa by increasing [Ca2+] was strongly reduced by HDM, as well as by the presence of La3+. (6) These results suggest, that HDM is bound irreversibly to Ca2+ and La3+ binding sites of the membrane that affect the size of INa. These sites are different from Ca2+ (or La3+) binding sites acting on the gating mechanism. (7) The potassium currents were also irreversibly reduced by HDM-treatment. This effect, however, was different for inward and outward currents; for inward currents the IK remaining was about 20% of its original size, while for outward currents IK was reduced only to about 65%. The time course of activation of IK was not affected by HDM-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Rack
M
M
Institut für Physiologische Chemie, Universität des Saarlandes, Federal Republic of Germany.
Drews
G
G
D000818:Animals; D004594:Electrophysiology; D006583:Hexadimethrine Bromide / Q000494:pharmacology*; D009412:Nerve Fibers / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D011893:Rana esculenta; D011901:Ranvier's Nodes / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D011073:Polyamines; D006583:Hexadimethrine Bromide; D012964:Sodium; D011188:Potassium