Page 46 - F. Cell biology

[F. Cell biology-27]

Cinnarizine inhibits Human Kv1.5 Channel Currents in the

Open state

Soobeen Hwang¹, Su-Hyun Jo¹

¹Physiology, Kangwon National University, Chuncheon 200-701, Korea, ²BIT Medical Convergence, Kangwon

National University, Chuncheon 200-701, Korea

Cinnarizine is specific calcium channel blocker that primarily works on the central vestibular system to interfere with
the signal transmission between vestibular apparatus of the inner ear and the vomiting center of the hypothalamus.

The Kv1.5 channel is a shaker-type, voltage-gated potassium channel encoded by the KCNA5 gene. It contributes

to the maintenance of cell membrane potential in a wide variety of tissues, including myocytes, pancreatic β-cells
and smooth muscle cells in the pulmonary vasculature. We examined the effect of cinnarizine on the human Kv1.5
channel using a Xenopus oocyte expression system and a two-microelectrode voltage clamp technique. We

examined the reversibility of cinnarizine inhibition of Kv1.5 currents. Inhibition was reversible even after washing for
40 min, peak currents reversed by 100%, steady-state reversed by 100%. Cinnarizine inhibited Kv1.5 use-dependent

manner. Peak current and steady-state currents are similar. Kv1.5 channel peak currents blockade increases at 1
second intervals and decrease at 15 second interval then recover blockade at 1 second interval. These results

suggested that cinnarizine inhibited Kv1.5 currents in the open state, via a non-genomic mechanism, cannot cross
plasma membrane, the effect may be short lasting.