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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Effects of aminoglycoside antibiotics on calcium action potentials and calcium channel currents
1Departamento de Farmacologia Básica e Clinica, Universidade Federal do Rio de Janeiro, Brasil.
Abstract:
The author reviews work from his laboratory on the effects of neomycin and streptomycin on the Ca(2+)-dependent electrogenesis of crustacean muscle fibers and on two distinct Ca2+ channel currents of pituitary cells. The data indicate that these aminoglycosides inhibit the graded electrogenesis and the action potentials of crustacean muscle; these effects are accompanied by inhibition of tension development upon membrane depolarization. Increasing the extracellular Ca2+ concentration reverses the aminoglycoside-induced blockade of the Ca(2+)-dependent electrogenesis of the muscle fibers. Neomycin blocked both the transient (T-type) and the slowly-inactivating (L-type) Ca2+ currents of clonal pituitary GH3 cells, studied with the whole cell modality of the patch clamp technique. The blockade of these currents was not modulated by activation or inactivation of the channels. Neomycin inhibited also the currents conveyed by Na+ through the slowly-inactivating Ca2+ in cells equilibrated with Ca(2+)-free media. Interpretation of these data led to the suggestion that the blockade of Ca2+ currents by neomycin (and other aminoglycosides) cannot be explained by competition with Ca2+ ions for binding to high affinity transition sites within the Ca2+ channel path.
Insights
Neomycin and streptomycin inhibit calcium channel currents in crustacean muscle and pituitary cells. These aminoglycosides block calcium currents, affecting muscle contraction and cell electrogenesis, with effects reversible by increasing extracellular calcium.
Area of Science:
- Pharmacology
- Neuroscience
- Cell Biology
Background:
- Aminoglycosides like neomycin and streptomycin are known for their antibiotic properties.
- Their effects on cellular electrogenesis and ion channels are not fully understood.
- Calcium (Ca2+) channels play critical roles in muscle contraction and hormone release.
Purpose of the Study:
- To investigate the effects of neomycin and streptomycin on Ca2+-dependent electrogenesis in crustacean muscle.
- To examine the impact of these aminoglycosides on distinct Ca2+ channel currents in pituitary cells.
- To elucidate the mechanism by which aminoglycosides block Ca2+ channels.
Main Methods:
- Electrophysiological recordings of crustacean muscle fibers.
- Patch clamp technique (whole-cell modality) on clonal pituitary GH3 cells.
- Investigation of Ca2+ and Na+ currents under varying extracellular Ca2+ concentrations.
Main Results:
- Neomycin and streptomycin inhibited graded electrogenesis and action potentials in crustacean muscle, reducing tension development.
- Increasing extracellular Ca2+ reversed the inhibitory effects of aminoglycosides on muscle fiber electrogenesis.
- Neomycin blocked both T-type and L-type Ca2+ currents in pituitary cells, independent of channel gating, and also inhibited Na+ currents.
Conclusions:
- Aminoglycosides, including neomycin, significantly disrupt Ca2+-dependent electrogenesis in muscle and pituitary cells.
- The blockade of Ca2+ currents by neomycin is not explained by simple competition with Ca2+ ions.
- These findings suggest a more complex interaction of aminoglycosides with ion channel function.
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