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Muscarinic receptor activation induces a prolonged post-stimulus afterdepolarization with a conductance decrease in

A Constanti¹, G Bagetta

¹Department of Pharmacology, School of Pharmacy, London, U.K.

Neuroscience Letters

|September 30, 1991

Summary

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Oxotremorine-M (OXO-M) causes sustained firing in guinea-pig cortical neurons by inducing a novel outward potassium current. Calcium entry during depolarization slowly deactivates this current, contributing to neuronal excitation.

Area of Science:

Neuroscience
Neurophysiology
Pharmacology

Background:

Muscarinic agonists like oxotremorine-M (OXO-M) are known to modulate neuronal activity.
Understanding the mechanisms of persistent neuronal excitation is crucial for comprehending brain function.

Purpose of the Study:

To investigate the persistent excitation of guinea-pig olfactory cortical neurons induced by OXO-M.
To elucidate the ionic mechanisms underlying the slow afterdepolarization (sADP) and sustained firing.

Main Methods:

In vitro electrophysiology on guinea-pig olfactory cortical neurons.
Voltage clamp techniques to analyze ionic currents (IADP).
Pharmacological manipulation using various ion channel blockers and solution compositions.

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Main Results:

OXO-M (10-20 microM) induced a slowly-decaying afterdepolarization (sADP) and sustained repetitive firing.
A slow inward current (IADP) was observed, behaving like a K(+)-mediated tail current but with decreased membrane conductance.
IADP was insensitive to TTX, Ba2+, Cs+, 4-AP, but blocked by TEA and TBA.
OXO-M response and IADP were reduced by Cd2+ or Ca(2+)-free solution, indicating Ca(2+) influx dependence.

Conclusions:

OXO-M induces a novel outward K+ current that is slowly deactivated by Ca(2+) influx during depolarization.
Summation of IADP tail currents likely contributes to sustained muscarinic excitation in mammalian cortical neurons.