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...
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Published in | Brain research Vol. 873; no. 1; pp. 46 - 53 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Elsevier B.V
04.08.2000
Amsterdam Elsevier New York, NY |
Subjects | |
Online Access | Get full text |
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Summary: | 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 α-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. |
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ISSN: | 0006-8993 1872-6240 |
DOI: | 10.1016/S0006-8993(00)02469-0 |