Electrogenic pump (Na+/K(+)-ATPase) activity in rat optic nerve.
Rat optic nerves were studied in a sucrose gap chamber in order to study the origin of a late afterhyperpolarization that follows repetitive activity. The results provide evidence for electrogenic pump (Na+/K(+)-ATPase) activity in central nervous system myelinated axons and demonstrate an effect on axonal excitability. Repetitive stimulation (25-200 Hz; 200-5000 ms) led to a prolonged, temperature-dependent post-train afterhyperpolarization with duration up to about 40 s. The post-train afterhyperpolarization was blocked by the Na+/K(+)-ATPase blockers strophanthidin and ouabain, and the substitution of Li+ for Na+ in the test solution, which also blocks Na+/K(+)-ATPase. The peak amplitude of the post-train afterhyperpolarization was minimally changed by the potassium-channel blocker tetraethylammonium (10 mM), and the Ca2(+)-channel blocker CoCl2 (4 mM). Hyperpolarizing constant current did not reverse the afterhyperpolarization. The amplitude of the hyperpolarization was increased in the presence of the potassium-channel blocker 4-aminopyridine (1 mM). In the presence of 4-amino-pyridine, the post-train hyperpolarization was much reduced by strophanthidin, except for a residual early component lasting several hundred milliseconds which was blocked by the potassium-channel blocker tetraethylammonium. This finding indicates that after exposure to 4-aminopyridine, repetitive stimulation leads to activation of a tetraethylammonium-sensitive K(+)-channel that contributes during the first several hundred milliseconds to the post-train afterhyperpolarization. The amplitude of the compound action potential elicited by a single submaximal stimulus during the post-train hyperpolarization was smaller than that of the control response. The decrement in amplitude was not present under identical stimulation conditions when the post-train hyperpolarization was blocked by strophanthidin, indicating that the hyperpolarization associated with repetitive stimulation reduced excitability.(ABSTRACT TRUNCATED AT 250 WORDS)
Gordon
T R
TR
Department of Neurology, Yale University School of Medicine, West Haven, CT 06516.
Kocsis
J D
JD
Waxman
S G
SG
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D009900:Optic Nerve / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013327:Strophanthidin / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D003035:Cobalt; D010042:Ouabain; D013327:Strophanthidin; D019789:Tetraethylammonium; D008094:Lithium; D015761:4-Aminopyridine; D000254:Sodium-Potassium-Exchanging ATPase; C018021:cobaltous chloride; D011188:Potassium