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Polyene antibiotics increase the ionic permeability of synaptosomal plasma membranes
O Raatikainen1, R A Kauppinen, H Komulainen
1Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
Biochemical Pharmacology
|May 1, 1991
Summary
Heptaene antibiotics like candicidin and amphotericin B increase calcium influx and respiration in nerve terminals by affecting ion permeability. These effects are likely due to non-specific leaks through polyene-cholesterol channels and increased sodium permeability.
Area of Science:
- Neuropharmacology
- Biochemistry
- Cell Biology
Background:
- Heptaene antibiotics are antifungal agents.
- Cerebral cortical nerve terminals (synaptosomes) are crucial for neurotransmission.
Purpose of the Study:
- To investigate the effects of candicidin and amphotericin B on isolated cerebral cortical nerve terminals.
- To elucidate the mechanisms underlying the action of these antifungal agents on synaptosomal function.
Main Methods:
- Incubation of synaptosomes with candicidin or amphotericin B.
- Measurement of intrasynaptosomal free Ca2+ levels.
- Assessment of synaptosomal respiration rate.
- Monitoring of plasma and mitochondrial membrane potentials.
Main Results:
- Candicidin and amphotericin B significantly increased intrasynaptosomal free Ca2+.
- These antibiotics also elevated synaptosomal respiration rate, independent of extracellular Ca2+.
- Candicidin induced dose-dependent plasma membrane depolarization, with minimal effect on mitochondrial potential.
Conclusions:
- Heptaene polyenes enhance synaptosomal ionic permeability, leading to increased Ca2+ influx and accelerated respiration.
- Calcium influx likely occurs via non-specific leaks through polyene-cholesterol channels.
- Accelerated respiration is linked to increased Na+ permeability, stimulating Na+, K+-ATPase activity and energy demand.