M-Current Suppression, Seizures and Lipid Metabolism: A Potential Link Between Neuronal Kv7 Channel Regulation and Dietary Therapies for Epilepsy.

Naoto Hoshi

doi:10.3389/fphys.2020.00513

Abstract

Neuronal Kv7 channel generates a low voltage-activated potassium current known as the M-current. The M-current can be suppressed by various neurotransmitters that activate Gq-coupled receptors. Because the M-current stabilizes membrane potential at the resting membrane potential, its suppression transiently increase neuronal excitability. However, its physiological and pathological roles in vivo is not well understood to date. This review summarizes the molecular mechanism underlying M-current suppression, and why it remained elusive for many years. I also summarize how regulation of neuronal Kv7 channel contributes to anti-seizure action of valproic acid through inhibition of palmitoylation of a Kv7 channel binding protein, and discuss about a potential link with anti-seizure mechanisms of medium chain triglyceride ketogenic diet.

Highlights

The M-current is a low voltage-activated potassium current generated by combination of neuronal KCNQ/Kv7 subunits (Kv7.2, 7.3, 7.4, and 7.5; Jentsch, 2000; Delmas and Brown, 2005; Greene and Hoshi, 2017)
Because there were no tools to prevent M-current suppression until very recently, physiological and pathological roles of M-current suppression in vivo are not well understood. Since this is a special issue for Kv7 channels covering various aspects, this review will focus on M-current suppression and its contribution to anti-seizure action of valproic acid
AKAP79/150 locates at the inner surface of the plasma membrane through PIP2 binding and attached fatty acid by protein palmitoylation (Dell’Acqua et al, 1998; Wong and Scott, 2004; Keith et al, 2012)

Summary

Introduction

The M-current is a low voltage-activated potassium current generated by combination of neuronal KCNQ/Kv7 subunits (Kv7.2, 7.3, 7.4, and 7.5; Jentsch, 2000; Delmas and Brown, 2005; Greene and Hoshi, 2017). AKAP79/150 locates at the inner surface of the plasma membrane through PIP2 binding and attached fatty acid by protein palmitoylation (Dell’Acqua et al, 1998; Wong and Scott, 2004; Keith et al, 2012). This Kv7.2-AKAP79/150calmodulin complex provides a molecular mechanism illustrating calcium-induced M-current suppression.

Results

Conclusion