ANTIARRHYTHMIC CALCIUM CHANNEL BLOCKER VERAPAMIL INHIBITS TREK CURRENTS
IN SYMPATHETIC NEURONS.
Abstract
Background and Purpose: Verapamil, a drug widely used in certain cardiac
pathologies, exert its therapeutic effect mainly through the blockade of
cardiac L-type calcium channels. However, we also know that both
voltage-dependent and certain potassium channels are blocked by
verapamil. Because sympathetic neurons of the superior cervical ganglion
(SCG) are known to express a good variety of potassium currents, and to
finely tune cardiac activity, we speculated that the effect of verapamil
on these SCG potassium channels could explain part of the therapeutic
action of this drug. To address this question, we decided to study, the
effects of verapamil on three different potassium currents observed in
SCG neurons: delayed rectifier, A-type and TREK (a subfamily of K2P
channels) currents. We also investigated the effect of verapamil on the
electrical behavior of sympathetic SCG neurons. Experimental Approach:
We employed the Patch-Clamp technique to mouse SCG neurons in culture.
Key Results: We found that verapamil depolarizes of the resting membrane
potential of SCG neurons. Moreover, we demonstrated that this drug also
inhibits A-type potassium currents. Finally, and most importantly, we
revealed that the current driven through TREK channels is also inhibited
in the presence of verapamil. Conclusion and Implications: We have shown
that verapamil causes a clear alteration of excitability in sympathetic
cells. This fact undoubtedly leads to an alteration of the
sympathetic-parasympathetic balance which may affect cardiac function.
Therefore, we propose that these possible peripheral alterations in the
autonomic system should be taken into consideration in the prescription
of this drug.