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) is activated, the channel closes. The M-channel is a PIP
2-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. 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
Gq 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 ...
. Specifically, the hydrolysis of PIP
2 to IP
3. This hydrolysis causes PIP
2, which is bound to the membrane, to become IP
3 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 PIP
2.
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 ...
inherited form of
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
. There are three known genetic causes of BFNE, two being in the channels
KCNQ2 and
KCNQ3.
References
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Electrophysiology
Neurophysiology