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Anti-caries DNA vaccine-induced secretory immunoglobulin A antibodies inhibit formation of Streptococcus mutans biofilms in vitro

	author = {Li Huang and Qing-an Xu and Chang Liu and Ming-wen Fan and Yu-hong Li},
	title = {Anti-caries DNA vaccine-induced secretory immunoglobulin A antibodies inhibit formation of Streptococcus mutans biofilms in vitro},
	journal = {Acta Pharmacologica Sinica},
	volume = {34},
	number = {2},
	year = {2016},
	keywords = {},
	abstract = {Hui CHEN1, Dong ZHANG1, Sheng-ping CHAO1, Jiang-hua REN1, *, Lin XU2, Xue-jun JIANG2, Shi-min WANG2

1Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430073, China
Aim: To study the effects of Na+ channel blocker flecainide and L-type Ca2+ channel antagonist verapamil on the voltage-gated fKv1.4ΔN channel, an N-terminal-deleted mutant of the ferret Kv1.4 K+ channel.

Methods: fKv1.4ΔN channels were stably expressed in Xenopus oocytes.  The K+ currents were recorded using a two-electrode voltage-clamp technique.  The drugs were administered through superfusion.

Results: fKv1.4ΔN currents displayed slow inactivation, with a half-inactivation potential of -41.74 mV and a slow recovery from inactivation (τ=1.90 s at -90 mV).  Flecainide and verapamil blocked the currents with IC50 values of 512.29±56.92 and 260.71±18.50 μmol/L, respectively.  The blocking action of the drugs showed opposite voltage-dependence: it was enhanced with depolarization for flecainide, and was attenuated with depolarization for verapamil.  Both the drugs exerted state-dependent blockade on fKv1.4ΔN currents, but verapamil showed a stronger use-dependent blockage compared with flecainide.  Flecainide accelerated the C-type inactivation rate without affecting the recovery kinetics and the steady-state activation.  Verapamil also accelerated the inactivation kinetics of the currents, but unlike flecainide, it affected both the recovery and the steady-state activation, causing slower recovery of fKv1.4ΔN channel and a depolarizing shift of the steady-state activation curve.

Conclusion: The results demonstrate that widely used antiarrhythmic drugs flecainide and verapamil substantially inhibit fKv1.4ΔN channels expressed in Xenopus oocytes by binding to the open state of the channels.  Therefore, caution should be taken when these drugs are administered in combination with K+ channel blockers to treat arrhythmia.

Keywords: Kv1.4; fKv1.4ΔN channel; Xenopus oocytes; antiarrhythmic drugs; flecainide; verapamil; activation; C-type inactivation; Na+ channel blockers; Ca2+ channel antagonists
We thank Dr Rasmusson (University at Buffalo, SUNY, USA) for the fKv1.4ΔN cDNA. 
* To whom correspondence should be addressed.
Received 2012-04-07    Accepted 2012-09-24},
	issn = {1745-7254},	url = {}