4-aminopyridine, a specific blocker of K(+) channels, inhibited inward Na(+) current in rat cerebellar granule cells.
The effects of 4-aminopyridine (4-AP), a specific blocker of outward K(+) current, on voltage-activated transient outward K(+) current (I(K(A))) and inward Na(+) current (I(Na)) were investigated on cultured rat cerebellar granule cells using the whole cell voltage-clamp technique. At the concentration of 1-5 mM, 4-AP inhibited both I(K(A)) and I(Na). It reduced the amplitude of peak Na(+) current without significant alteration of the steady-state activation and inactivation properties. The inhibitory effect was not enhanced by repeated depolarizing pulses (0.5 or 0.1 Hz), suggesting that the binding affinity of 4-AP on Na(+) channels is state-independent. In contrast, the effect of 4-AP on Na(+) channels appeared to be voltage-dependent, the weaker inhibition occurred at more depolarization. Moreover, 4-AP slowed both the activation and inactivation kinetics of Na(+) current. These effects were similar to those induced by alpha-scorpion toxin and sea anemone toxins on Na(+) channels in other cell model. Our data demonstrate for the first time that 4-AP is able to block not only A-type K(+) channels, but also Na(+) channels in rat cerebellar granule cells. It is concluded that the inhibition exerted by 4-AP on Na(+) current likely differs from that provoked by local anesthetics. The possibility that the binding site of neurotoxin receptor 3 may be involved is discussed.
Mei
Y A
YA
Center for brain science research and Liren laboratory, School of Life Sciences, Fudan University, Shanghai, PR China. yamei@fudan.edu.cn
Wu
M M
MM
Huan
C L
CL
Sun
J T
JT
Zhou
H Q
HQ
Zhang
Z H
ZH
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004553:Electric Conductivity; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000037:antagonists & inhibitors* / Q000502:physiology*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012964:Sodium; D015761:4-Aminopyridine