M Channels Containing KCNQ2 Subunits Modulate Norepinephrine, Aspartate, and GABA Release from Hippocampal Nerve Terminals

Abstract

KCNQ subunits encode for the M current (I KM)

Muscarinic receptor type 1 (M1) stimulation, probably through KCNQ/Kv7 channel closure, increases spontaneous GABA release at the dendrodendritic synapse in the mouse accessory olfactory bulb

“…Inhibition of carbachol's action by the KCNQ channel openers retigabine or diclofenac suggested that carbachol acts via the down-regulation of KCNQ channels. The down-regulation of KCNQ channels increases transmitter release (Lechner et al, 2003;Martire et al, 2004;Peretz et al, 2007;, and the link between muscarinic stimulation and KCNQ channel down-regulation is well-established . It is therefore probable that carbachol down-regulates the activity of KCNQ channels in the granule cells and, through increased membrane depolarization, increases the open probability of membrane calcium channels, resulting in an increase in synaptic vesicle release.…”

Genotype–phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of K v 7.2 potassium channel subunits

“…By contrast, the 16-mV positive shift in V 1/2 observed upon incorporation of a single K V 7.2 R6Q subunit in heteromeric configuration with K V 7.2 and K V 7.3 subunits to recapitulate the genotype of the individual affected with K V 7.2 encephalopathy (8), is the most dramatic among the functional changes described in K V 7.2 channelopathies (33). More dramatic effects of the R6Q mutation compared with the R6W mutation were also observed in homomeric K V 7.2 channels, which have been suggested to contribute to I KM diversity at Ranvier nodes in central and peripheral fibers (18,19) and, possibly, presynaptic nerve terminals (20). Notably, in rat superior cervical ganglion neurons, K v 7.2 homomers appear to be more prevalent during early development (21).…”

“…Given that homomeric K V 7.2 channels might contribute to I KM diversity at some neuronal sites (18)(19)(20) and might be more prevalent during early development (21), the effects of both R6 K V 7.2 mutations were also studied in heteromeric configuration with only K V 7.2 subunits (1:1 ratio). Under this experimental condition, which generated a larger proportion of channels containing two mutant subunits, the gating changes observed were intermediate between homomeric (four mutant subunits) and single heteromeric subunits (Table 1); also under this experimental condition, R6W-containing channels displayed milder gating changes compared with R6Q-substituted channels (Fig.…”

Protective Role of Kv7 Channels in Oxygen and Glucose Deprivation-Induced Damage in Rat Caudate Brain Slices

“…8,12 Pharmacological modulation of the M current modifies depolarization-induced neurotransmitter release in different brain areas. 13 In particular, the K v 7 activator retigabine, a recently marketed antiepileptic drug used as an adjunctive treatment in patients with refractory epilepsy, was able to decrease dopamine release from isolated striatal nerve terminals exposed to high extracellular K + concentrations. 14 In addition, while some studies have shown that K v 7 activators reduced neuronal damage in hippocampal brain slices, 15,16 others found that M-current activation increased death in hippocampal cultured neurons.…”