Physostigmine and acetylcholine differentially activate nicotinic receptor subpopulations in Locusta migratoria neurons.

Abstract:

:The effects of acetylcholine (ACh) and physostigmine (PHY) on thoracic ganglion neurons of Locusta migratoria were investigated using whole-cell and cell-attached voltage clamp. ACh activated whole-cell currents with variable amplitudes, time course and ion channel block between cells, suggesting differential expression of nicotinic acetylcholine receptor (nAChR) subtypes. This was supported by selective block of the peak of the currents by the alpha7-specific alpha-conotoxin ImI. PHY at 100 microM evoked smaller whole-cell currents with variable amplitudes and marginal desensitization. The PHY/ACh amplitude ratio varied between cells, and was positively related to the time constant of decay of the ACh response. EC50 values for the peak amplitude of the ACh- and PHY-induced currents were 50 microM and 3 microM, respectively. Both agonists activated nAChR, indicated by equal voltage-dependence and reversal potentials and the same pharmacological properties of ACh and PHY responses. In addition, PHY and ACh induced ion channel block. Co-application and cross-desensitization experiments showed that ACh and PHY activate the same nAChR subpopulations. Both agonists activated nicotinic single channels with three conductance levels, which were equal for ACh and PHY, indicating activation of the same nAChR subtypes by both agonists. However, for all levels PHY displayed a lower open probability than ACh. Taken together, different whole-cell responses appear to originate from differential activation, desensitization and ion channel block by ACh and PHY of distinct nAChR populations.

journal_name

Brain Res

journal_title

Brain research

authors

van den Beukel I,van Kleef RG,Zwart R,Oortgiesen M

doi

10.1016/s0006-8993(98)00007-9

subject

Has Abstract

pub_date

1998-04-13 00:00:00

pages

263-73

issue

2

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(98)00007-9

journal_volume

789

pub_type

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