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.

Background and Purpose: Cardiovascular side effects from varenicline, and a case report of a hypertensive crisis event in a patient with pheochromocytoma being treated with varenicline, have been reported. The goal of the present study was to determine if such side effects might derive, in part, from increased exocytosis of secretory vesicles and subsequent catecholamine release triggered by varenicline in chromaffin cells of the adrenal gland. Experimental Approach: We performed electrophysiological plasma membrane capacitance (Cm) and carbon fiber amperometry experiments to evaluate the effect of varenicline on exocytosis and catecholamine release, respectively, at concentrations reached during varenicline therapy (100 nM). Experiments were conducted in the absence or presence of nicotine, at plasma concentrations achieved right after smoking (250 nM) or steady-state concentrations (110 nM), in chromaffin cells of the adrenal gland obtained from human organ donors or rats. Key Results: Varenicline increased the exocytosis of secretory vesicles and the release of catecholamines from human chromaffin cells in the presence of nicotine. Comparable results were found using rat chromaffin cells; varenicline alone or in the presence of acute or steady-state concentrations of nicotine found in human plasma increased exocytosis. These effects were not due to an increase of Cm or currents triggered by the nicotinic agonists alone. Conclusion and Implications: Therapeutic concentrations of varenicline in the presence of nicotine increased exocytosis and catecholamine release from human chromaffin cells. These results should be taken into account in nicotine addiction therapies when varenicline is used.