M current is a type of noninactivating potassium current first discovered in bullfrog sympathetic ganglion cells. The ''M-channel'' is a voltage-gated K+ channel ( Kv7/KCNQ family) that is named after the receptor it is influenced by. The M-channel is important in raising the threshold for firing an action potential. It is unique because it is open at rest and even more likely to be open during depolarization. Furthermore, when the muscarinic acetylcholine receptor (

MAChR Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

) is activated, the channel closes. The M-channel is a PIP₂-regulated ion channel. Kv7 channels have a prominent expression throughout the brain.

Function

Actions of M-currents: "phasic-firing"

M-channels are the reason for slow depolarizations produced by ACh and LHRH in the autonomic ganglia and other specified areas. 1. Initial depolarization of a neuron increases likelihood that M-channels will open. 2. M-channels generate an outward potassium current (I_K). 3. Potassium efflux counteracts sodium influx in action potential (AP). Overall result: full action potential is prevented.

Inhibition of M-current: "tonic-firing"

1 molecule of Acetylcholine (Ach) binds to

mAchR Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

. Potassium (K+) channels become more likely to be closed. Neuron becomes ''tonic-firing''. This reduction in M-current is coupled with the actions of the G_q

G-protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...

. Specifically, the hydrolysis of PIP₂ to IP₃. This hydrolysis causes PIP₂, which is bound to the membrane, to become IP₃ and dissociate from the membrane into the cytoplasm. When M-current is restored, it moves back to the membrane. There is some evidence for different theories of how M-channel activity is directly affected by PIP₂.

Clinical implications

Benign familial neonatal seizures (BFNE) is an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

inherited form of

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

. There are three known genetic causes of BFNE, two being in the channels

KCNQ2 Kv7.2 (KvLQT2) is a voltage- and lipid-gated potassium channel protein coded for by the gene KCNQ2. It is associated with benign familial neonatal epilepsy. Function The M channel is a slowly activating and deactivating potassium channel th ...

and

KCNQ3 Kv7.3 (KvLQT3) is a potassium channel protein coded for by the gene KCNQ3. It is associated with benign familial neonatal epilepsy. The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regul ...

References

{{reflist, colwidth=30em Electrophysiology Neurophysiology