Page 2 - Q. Neuroscience

[Q. Neuroscience-1]

Inhibitory effect of antidepressant metergoline on Kv1.4

channel

Jun-Ho Lee¹

¹Biotechonology, Chonnam National University, Gwangju 60086, Korea

Voltage-gated potassium channels (VGKCs) are transmembrane ion channels specific for potassium. Currently there
are nine kinds of VGKCs. Kv1.4 is one of shaker-related potassium channels. It is a representative alpha subunit of
potassium channels that can inactivate A type-currents, leading to N pattern inactivation. Inactivation of Kv channels

plays an important role in shaping electrical signaling properties of neuronal and muscular cells. The shape of N

pattern inactivation can be modified by removing the N-terminal (NT) domain which results in non-inactivated
currents and C pattern inactivation. Our results revealed that treatment with metergoline inhibited NT deleted Kv1.4
mutant channel activity in a concentration-dependent manner which was reversible. Interestingly, metergoline

treatment induced little effects on the outward peak current in the deleted Kv1.4 mutant channel. This result further
shows that metergoline might interact with Lys532 residue and then accelerate C pattern inactivation of Kv1.4

channels with channel type specificity. Taken together, these results demonstrate the molecular basis involved in the
effect of metergoline, an ergot alkaloid, on human Kv1.4 channel, providing a novel interaction ligand.