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Printable Handouts
Navigable Slide Index
- Introduction
- What is 'M-current'?
- The M-current of a frog sympathetic neuron
- M-channels opening range
- Why 'M' current?
- The KCNQ/Kv7 family of potassium channels
- The M-channels' subunits
- How muscarinic receptors close M-channels
- Muscarinic receptors use 'remote signaling'
- The 'PIP2 hypothesis'
- M-channels depend on PIP2 to open
- Acetylcholine reduces the amount of PIP2
- PIP2 hydrolysis in a living neuron
- M-current inhibition by a muscarinic agonist
- Other M-current inhibitors
- Additional mechanisms of M-channel regulation
- Functions of M-channels
- M-current clamps membrane potential
- M-current reduces neurons' excitability
- M-current inhibition in synaptic transmission
- Nicotinic transmission in a rat ganglion
- Muscarinic transmission in a rat ganglion
- Muscarinic synaptic excitation in a rat ganglion
- Sensory systems and pain
- M-channel subunits in rat DRG
- M-current in rat nociceptive sensory neurons
- M-channel block's influence
- Peripheral nerves and hyper-excitability
- M-channels in mammalian nodes of Ranvier
- M-current block and nerve firing
- Electromyogram from rat tail muscle
- Mutations in the human KCNQ2 gene
- Effect of mutation in KCNQ2
- KCNQ2 mutation and channel behaviour
- Hippocampus and epilepsy
- Reduced spike frequency accommodation
- Enhanced spike after-depolarization - burst firing
- Spontaneous firing in hippocampal neurons
- M-current inhibition and spontaneous firing
- Location of M-channels
- Kv7 channels bind ankyrin-G via ABP
- Disruption of ankyrin-binding
- ABP reduces threshold for action potential
- M-channels and epilepsy
- BFNC mutation reduces M-current
- BFNC mutation (movie)
- Cerebral cortex: attention and cognition
- Methacholine inhibits M-current
- Facilitation of action potential discharges
- Cerebral cortex neurons and the nucleus basalis
- Cholinergic system - attention-directing modality
- Attention directing in the visual cortex
- Other points of interest
- Acknowledgments
Topics Covered
- Basic properties
- Molecular composition
- Inhibition by acetycholine and mechanism of inhibition
- Functions: membrane potential clamp
- Control of action potential discharges
- Control of nociceptive sensory excitation
- Suppression of repetitive discharges at nodes of Ranvier
- Regulation of action potential threshold at axon initial segment
- Suppression of epileptiform discharges in central neurons
- Contribution of M-channel inhibition to cholinergic excitation
Talk Citation
Brown, D.A. (2020, May 1). M-current and its role in neuronal physiology [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/UOFQ3731.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. David A. Brown has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 39:08 min
- Update Interview Duration: 7:16 min
A selection of talks on Neuroscience
Transcript
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0:00
Hello, my name is David Brown.
I'm a professor of pharmacology,
Department of Neuroscience, Physiology,
and Pharmacology at
University College London.
I'm going to talk to you
about the-M current and
its role in neuronal physiology.
0:14
What is the M-current?
It's a species of voltage-gated
potassium current.
It was first seen in frog neurons,
but is present in many mammalian and
human peripheral and central neurons,
and in the nerve fibres.
It is inhibited by stimulating
muscarinic acetylcholine receptors,
that's how it got its name 'M',
though in fact it can be inhibited by
stimulating other receptors so long as
they're linked to the G-protein, Gq.
Channels are composed of subunits of
the Kv7 family, mainly Kv7.2 and 7.3.
The function is to stabilise membrane
potential and to control excitability, so
that when the current is inhibited,
neurons are depolarised and
they show an increased excitability.
In this talk, I'll illustrate these
points with some pictures of experimental
recordings, just to give you a feel for
how the current works, and
how it affects nerve cell behavior.
1:09
This shows one of our original recordings
of the M-current in a frog sympathetic
neuron, made using a dual
electro-voltage clamp.
One electrode sets the voltage, and the
other one monitors the membrane current.
In the record on the right,
the cell membrane potential is held at -60
millivolts to start with, and then it's
set for one second to -30 millivolts.
This generates the outward
current shown by the arrow.
It has two main features, firstly,
it activates rather slowly over tens or
hundreds of milliseconds.
Secondly, it does not show the
inactivation characteristic of many other
voltage-gated potassium currents, as,
once switched on, the current stays on for
many seconds or minutes,
generating a steady outward current.