Inhibition of Na+ channel currents in rat myoblasts by 4-aminopyridine.
Our previous study revealed that 4-aminopyridine (4-AP), a specific blocker of A-type current, could also inhibit inward Na+ currents (I(Na)) with a state-independent mechanism in rat cerebellar granule cells. In the present study, we report an inhibitory effect of 4-AP on voltage-gated and tetrodotoxin (TTX)-sensitive I(Na) recorded from cultured rat myoblasts. 4-AP inhibited I(Na) amplitude in a dose-dependent manner between the concentrations of 0.5 and 10 mM without significant alteration in the activation or inactivation kinetics of the channel. By comparison to the 4-AP-induced inhibitory effect on cerebellum neurons, the inhibitory effect on myoblasts was enhanced through repetitive pulse and inflected by changing frequency. Specifically, the lower the frequency of pulse, the higher the inhibition observed, suggesting that block manner is inversely use-dependent. Moreover, experiments adding 4-AP to the intracellular solution indicate that the inhibitory effects are localized inside the cell. Additionally, 4-AP significantly modifies the properties of steady-state activation and inactivation kinetics of the channel. Our data suggest that the K+ channel blocker 4-AP inhibits both neuron and myoblast Na+ channels via different mechanisms. These findings may also provide information regarding 4-AP-induced pharmacological and toxicological effects in clinical use and experimental research.
Lu
Bo-Xun
BX
Center for Brain Science Research, School of Life Sciences, Fudan University, Shanghai 200433, China.
Liu
Lin-Yun
LY
Liao
Lei
L
Zhang
Zhi-Hong
ZH
Mei
Yan-Ai
YA
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D015761:4-Aminopyridine