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Selective drug action on two Ca2+ uptake processes in normal and hyperexcitable presynaptic membrane
Drugs Under Experimental and Clinical Research
|January 1, 1986
Summary
Aminopyridines induce repetitive firing in bullfrog sympathetic ganglia by increasing calcium-dependent transmitter release. Calcium channel blockers selectively inhibit this repetitive firing, suggesting distinct calcium uptake pathways for normal transmission and hyperexcitability.
Area of Science:
- Neuroscience
- Cellular Physiology
- Pharmacology
Background:
- Synaptic transmission relies on Ca2+-dependent presynaptic and Na+-dependent postsynaptic excitability.
- Aminopyridines enhance presynaptic Ca2+ influx, leading to repetitive postsynaptic spike responses (SBR).
Purpose of the Study:
- To investigate the role of separate presynaptic Ca2+ uptake processes in synaptic transmission and SBR.
- To examine the effects of calcium channel blockers (CCBs) on aminopyridine-induced SBR and normal synaptic transmission.
Main Methods:
- Utilized in vitro bullfrog sympathetic ganglia.
- Administered aminopyridines (e.g., 3,4-DAP) to induce SBR.
- Manipulated extracellular Ca2+ concentrations ([Ca2+]0).
- Applied calcium channel blockers (verapamil, diltiazem) at varying concentrations.
Main Results:
- Reduced [Ca2+]0 selectively abolished 3,4-DAP-induced SBR before affecting primary synaptic transmission.
- Verapamil and diltiazem selectively inhibited SBR at lower concentrations than those blocking normal transmission.
- CCBs demonstrated concentration-dependent selectivity in stabilizing hyperexcitable presynaptic membranes.
Conclusions:
- Evidence supports distinct presynaptic Ca2+ uptake mechanisms for normal transmission and SBR.
- CCBs exhibit selective blockade of Ca2+ channels involved in SBR, distinct from those mediating primary transmission.
- These findings offer insights into the differential regulation of presynaptic Ca2+ dynamics.