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Cited by 499Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyReceptor Mechanisms and Signaling

Mechanisms of action of acetylcholine in the guinea‐pig cerebral cortex in vitro.

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McCormick, D A, Prince, D A·1986·The Journal of Physiology
DOI 10.1113/jphysiol.1986.sp016112PMC PMC1182754
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Abstract

The mechanisms of action of acetylcholine (ACh) in the guinea‐pig neocortex were investigated using intracellular recordings from layer V pyramidal cells of the anterior cingulate cortical slice. At resting membrane potential (Vm = ‐80 to ‐70 mV), ACh application resulted in a barrage of excitatory and inhibitory post‐synaptic potentials (p.s.p.s) associated with a decrease in apparent input resistance (Ri). ACh, applied to pyramidal neurones depolarized to just below firing threshold (Vm = ‐65 to ‐55 mV), produced a short‐latency hyperpolarization concomitant with p.s.p.s and a decrease in Ri, followed by a long‐lasting (10 to greater than 60 s) depolarization and action potential generation. Both of these responses were also found in presumed pyramidal neurones of other cortical regions (sensorimotor and visual) and were blocked by muscarinic, but not nicotinic, antagonists. The ACh‐induced hyperpolarization possessed an average reversal potential of ‐75.8 mV, similar to that for the hyperpolarizing response to gamma‐aminobutyric acid (GABA; ‐72.4 mV) and for the i.p.s.p. generated by orthodromic stimulation (‐69.6 mV). This cholinergic inhibitory response could be elicited by ACh applications at significantly greater distance from the cell than the slow depolarizing response. Blockade of GABAergic synaptic transmission with solution containing Mn2+ and low Ca2+, or by local application of tetrodotoxin (TTX), bicuculline or picrotoxin, abolished the ACh‐induced inhibitory response but not the slow excitatory response. In TTX (or Mn2+, low Ca2+) the slow excitatory response possessed a minimum onset latency of 250 ms and was associated with a voltage‐dependent increase in Ri. Application of ACh caused short‐latency excitation associated with a decrease in Ri in eight neurones. The time course of this excitation was similar to that of the inhibition seen in pyramidal neurones. Seven of these neurones had action potentials with unusually brief durations, indicating that they were probably non‐pyramidal cells. ACh blocked the slow after‐hyperpolarization (a.h.p.) following a train of action potentials, occasionally reduced orthodromically evoked p.s.p.s, and had no effect on the width or maximum rate of rise or fall of the action potential. It is concluded that cholinergic inhibition of pyramidal neurones is mediated through a rapid muscarinic excitation of non‐pyramidal cells, resulting in the release of GABA. In pyramidal cells ACh causes a relatively slow blockade of both a voltage‐dependent hyperpolarizing conductance (M‐current) which is most active at depolarized membrane potentials, and the Ca2+‐activated K+ conductance underlying the a.h.p.(ABSTRACT TRUNCATED AT 400 WORDS)

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Authors
McCormick, D. A., & Prince, D. A.
ORCID
McCormick, D A
Venue
The Journal of Physiology
Publisher
Wiley
Published
1986-06
Volume
375
Issue
1
Pages
169-194
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.1986.sp016112
PMC
PMC1182754
OpenAlex
W2014630817
Cited by
499
References
39
Citations by year
2025: 2 · 2024: 6 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 9 · 2017: 8 · 2016: 9 · 2015: 3 · 2014: 10 · 2013: 13 · 2012: 16
FWCI
5.46
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS07331, NS12151)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
acetylcholine, cerebral cortex, pyramidal neurons, cholinergic inhibition, cholinergic stimulation, muscarinic receptors, nicotinic acetylcholine receptors, input resistance, postsynaptic potentials, GABAergic neurotransmission, afterhyperpolarization, action potential duration, cortical slices, guinea pig, tetrodotoxin, bicuculline, picrotoxin
MeSH terms
Acetylcholine, Action Potentials, Animals, Bicuculline, Cerebral Cortex, Female, gamma-Aminobutyric Acid, Glutamates, Guinea Pigs, Male, Synaptic Transmission, Neuromuscular Junction, Neurons, Tetrodotoxin, Time Factors, Glutamic Acid, In Vitro Techniques

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