Aminoglycoside antibiotics block voltage-dependent calcium channels in intact vertebrate nerve terminals.
Intrinsic and extrinsic optical signals recorded from the intact nerve terminals of vertebrate neurohypophyses were used to investigate the anatomical site and physiological mechanism of the antagonistic effects of aminoglycoside antibiotics on neurotransmission. Aminoglycoside antibiotics blocked the intrinsic light scattering signal closely associated with neurosecretion in the mouse neurohypophysis in a concentration-dependent manner with an IC50 of approximately 60 microM and the block was relieved by increasing [Ca2+]o. The rank order potency of different aminoglycoside antibiotics for blocking neurosecretion in this preparation was determined to be: neomycin greater than gentamicin = kanamycin greater than streptomycin. Optical recordings of rapid changes in membrane potential using voltage-sensitive dyes revealed that aminoglycoside antibiotics decreased the Ca(2+)-dependent after-hyperpolarization of the normal action potential and both the magnitude and after-hyperpolarization of the regenerative Ca2+ spike. The after-hyperpolarization results from a Ca-activated potassium conductance whose block by aminoglycoside antibiotics was also reversed by increased [Ca2+]o. These studies demonstrate that the capacity of aminoglycoside antibiotics to antagonize neurotransmission can be attributed to the block of Ca channels in the nerve terminal.
Parsons
T D
TD
Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia 19104-6085.
Obaid
A L
AL
Salzberg
B M
BM
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009411:Nerve Endings / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000493:pharmacokinetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D015220:Calcium Channels; D011188:Potassium; D002118:Calcium