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Int. J. Mol. Sci. 2018, 19(7), 1961; https://doi.org/10.3390/ijms19071961

Verapamil Inhibits TRESK (K2P18.1) Current in Trigeminal Ganglion Neurons Independently of the Blockade of Ca2+ Influx

1
Department of Neurosurgery, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju 52727, South Korea
2
Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea
3
Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, South Korea
*
Authors to whom correspondence should be addressed.
Received: 5 June 2018 / Revised: 27 June 2018 / Accepted: 2 July 2018 / Published: 4 July 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Tandem pore domain weak inward rectifier potassium channel (TWIK)-related spinal cord K+ (TRESK; K2P18.1) channel is the only member of the two-pore domain K+ (K2P) channel family that is activated by an increase in intracellular Ca2+ concentration ([Ca2+]i) and linked to migraines. This study was performed to identify the effect of verapamil, which is an L-type Ca2+ channel blocker and a prophylaxis for migraines, on the TRESK channel in trigeminal ganglion (TG) neurons, as well as in a heterologous system. Single-channel and whole-cell currents were recorded in TG neurons and HEK-293 cells transfected with mTRESK using patch-clamping techniques. In TG neurons, changes in [Ca2+]i were measured using the fluo-3-AM Ca2+ indicator. Verapamil, nifedipine, and NiCl2 inhibited the whole-cell currents in HEK-293 cells overexpressing mTRESK with IC50 values of 5.2, 54.3, and >100 μM, respectively. The inhibitory effect of verapamil on TRESK channel was also observed in excised patches. In TG neurons, verapamil (10 μM) inhibited TRESK channel activity by approximately 76%. The TRESK channel activity was not dependent on the presence of extracellular Ca2+. In addition, the inhibitory effect of verapamil on the TRESK channel remained despite the absence of extracellular Ca2+. These findings show that verapamil inhibits the TRESK current independently of the blockade of Ca2+ influx in TG neurons. Verapamil will be able to exert its pharmacological effects by modulating TRESK, as well as Ca2+ influx, in TG neurons in vitro. We suggest that verapamil could be used as an inhibitor for identifying TRESK channel in TG neurons. View Full-Text
Keywords: background potassium channel; calcium; trigeminal ganglions; verapamil background potassium channel; calcium; trigeminal ganglions; verapamil
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Park, H.; Kim, E.-J.; Ryu, J.H.; Lee, D.K.; Hong, S.-G.; Han, J.; Han, J.; Kang, D. Verapamil Inhibits TRESK (K2P18.1) Current in Trigeminal Ganglion Neurons Independently of the Blockade of Ca2+ Influx. Int. J. Mol. Sci. 2018, 19, 1961.

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