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Autonomic function in mice lacking alpha5 neuronal nicotinic acetylcholine receptor subunit.
Ningshan Wang1, Avi Orr-Urtreger, Joab Chapman
1Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, Israel.
The Journal of Physiology
|July 18, 2002
Summary
Neuronal acetylcholine nicotinic receptors (nAChR) alpha5 subunits modulate autonomic nervous system function. Mice lacking alpha5 subunits showed altered cardiac responses and increased sensitivity to certain drugs, highlighting their role in autonomic ganglia.
Area of Science:
- Neuroscience
- Pharmacology
- Autonomic Nervous System Research
Background:
- Neuronal acetylcholine nicotinic receptors (nAChRs) comprise 12 subunits, with specific subunits found in the autonomic nervous system (ANS).
- The alpha5 subunit of nAChRs possesses distinct biophysical and pharmacological characteristics.
- Understanding the role of alpha5 subunits is crucial for deciphering nAChR function in the ANS.
Purpose of the Study:
- To investigate the functional significance and pharmacological properties of nAChR alpha5 subunits within the ANS.
- To utilize alpha5 knockout (alpha5-/-) mice to elucidate the in vivo role of these subunits.
Main Methods:
- Generation and physiological assessment of mice lacking alpha5 nAChR subunits (alpha5-/-).
- Evaluation of thermoregulation, pupil size, resting heart rate, and response to cold stress.
- Assessment of cardiac parasympathetic ganglionic transmission and bradycardia response to vagal stimulation.
- Pharmacological testing with hexamethonium, cytisine, and epibatidine to determine effects on autonomic functions.
Main Results:
- Mice lacking alpha5 subunits exhibited normal physical and neurological development, thermoregulation, pupil size, and resting heart rate.
- alpha5-/- mice demonstrated resistance to cardiac arrest during high-frequency vagal stimulation compared to wild-type.
- Deficiency in alpha5 subunits significantly enhanced sensitivity to hexamethonium, blocking vagal stimulation-induced bradycardia.
- Ileal contractile responses to cytisine and epibatidine were significantly increased in alpha5-/- mice.
Conclusions:
- Alpha5 subunits play a critical role in modulating the affinity and sensitivity of native nAChRs to agonists and antagonists.
- The absence of alpha5 subunits impacts cardiac parasympathetic transmission and drug sensitivity in vivo.
- These findings imply that alpha5 subunits are key modulators of nAChR activity in autonomic ganglia.