M current is a type of noninactivating potassium current first discovered in bullfrog sympathetic ganglion cells.[1]
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 PIP2-regulated ion channel.[2] Kv7 channels have a prominent expression throughout the brain.[3]
M-current, also known as IM, is a type of voltage-gated potassium channel current that plays a crucial role in regulating neuronal excitability. It is named after the initial used for "muscarinic," reflecting its sensitivity to muscarinic acetylcholine receptor activation. This current was first described in sympathetic neurons but has since been found in various types of neurons throughout the nervous system.
The M-current is primarily carried by potassium ions (K+), contributing to the repolarization of the neuronal membrane potential following an action potential. Unlike other potassium currents, the M-current activates slowly and exhibits a relatively small conductance. This unique kinetic profile allows the M-current to exert fine control over neuronal firing patterns, particularly during sub-threshold membrane potential fluctuations.
The physiological significance of the M-current lies in its ability to regulate neuronal excitability and shape action potential firing patterns. By modulating the duration and frequency of action potentials, the M-current influences synaptic integration, neuronal synchronization, and network activity. Dysfunction of the M-current has been implicated in various neurological disorders, including epilepsy, neuropathic pain, and certain psychiatric conditions.
Pharmacological modulation of the M-current has emerged as a potential therapeutic strategy for treating neurological disorders characterized by aberrant neuronal excitability. Compounds that enhance M-current activity, such as retigabine, have shown promise in preclinical and clinical studies for the treatment of epilepsy and neuropathic pain. Conversely, inhibition of the M-current may be beneficial for conditions characterized by hypoexcitability, such as certain types of depression.
Understanding the mechanisms underlying M-current regulation and its effects on neuronal function remains an active area of research in neurophysiology and pharmacology. Further elucidating the roles of the M-current in health and disease could lead to the development of novel therapeutic interventions targeting neurological and psychiatric disorders.
Function[edit]
Actions of M-currents: "phasic-firing"[edit]
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 (IK). 3. Potassium efflux counteracts sodium influx in action potential (AP). Overall result: full action potential is prevented. [2] : 343
Inhibition of M-current: "tonic-firing"[edit]
1 molecule of Acetylcholine (Ach) binds to mAchR. Potassium (K+) channels become more likely to be closed. Neuron becomes tonic-firing. [2] : 343 This reduction in M-current is coupled with the actions of the Gq G-protein. 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.[2] : 229
Clinical implications[edit]
Benign familial neonatal seizures (BFNE) is an autosomal dominant inherited form of seizures. There are three known genetic causes of BFNE, two being in the channels KCNQ2 and KCNQ3.
References[edit]
- ^ Brown DA, Adams PR (February 1980). "Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone". Nature. 283 (5748): 673–6. Bibcode:1980Natur.283..673B. doi:10.1038/283673a0. PMID 6965523. S2CID 4238485.
- ^ a b c d Nicholls JG, Martin AR, Fuchs PA, Brown DA, Diamond ME, Weisblat DA (2012). From Neuron to Brain (Fifth ed.). pp. 229, 342.
- ^ Greene DL, Hoshi N (February 2017). "Modulation of Kv7 channels and excitability in the brain". Cellular and Molecular Life Sciences. 74 (3): 495–508. doi:10.1007/s00018-016-2359-y. PMC 5243414. PMID 27645822.