Related Experiment Videos
Separation of two pathways for calcium entry into chromaffin cells
L Gandía1, L F Casado, M G López
1Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
British Journal of Pharmacology
|May 1, 1991
Summary
This study differentiates calcium channels in adrenal chromaffin cells. Nicotinic receptor stimulation uses one channel type, while potassium depolarization may activate an additional channel, offering new drug targets.
Area of Science:
- Pharmacology
- Neuroscience
- Cell Biology
Background:
- Cultured bovine adrenal chromaffin cells are crucial for studying neurotransmitter release.
- Calcium (Ca) influx is a key event in stimulus-secretion coupling.
- Differentiating Ca channels activated by different stimuli is essential for understanding cellular responses.
Purpose of the Study:
- To investigate the pharmacological properties of calcium uptake pathways in bovine adrenal chromaffin cells.
- To determine if distinct calcium channels are involved in responses evoked by nicotinic receptor stimulation versus high potassium depolarization.
- To identify specific drug candidates that can selectively block these pathways.
Main Methods:
- Utilized cultured bovine adrenal chromaffin cells.
- Measured 45Ca uptake as a marker for Ca influx.
- Stimulated cells using 1,1-dimethyl-4-phenylpiperazinium (DMPP) for nicotinic receptor activation and high potassium (K) for depolarization.
- Assessed the effects of various drugs, including flunarizine, cadmium (Cd) ions, amiloride, guanethidine, nimodipine, and nisoldipine, on Ca uptake.
Main Results:
- Flunarizine and Cd ions blocked both DMPP- and K-evoked Ca uptake, suggesting a role in both pathways.
- Amiloride, guanethidine, nimodipine, and nisoldipine selectively inhibited DMPP-evoked Ca uptake, indicating distinct channel involvement.
- K-evoked Ca uptake showed partial or no inhibition by amiloride, guanethidine, nimodipine, and nisoldipine, suggesting the involvement of additional or different Ca channels.
- Pharmacological differences suggest distinct Ca uptake mechanisms activated by nicotinic receptors and K depolarization.
Conclusions:
- The nicotinic receptor-mediated Ca uptake pathway can be pharmacologically distinguished from the K+-activated pathway.
- Nicotinic receptor stimulation likely recruits a single type of Ca channel sensitive to flunarizine, Cd, amiloride, guanethidine, nimodipine, and nisoldipine.
- K+ depolarization may activate an additional Ca channel, distinct from the one activated by nicotinic receptors, which is sensitive to Cd and flunarizine but resistant to amiloride, guanethidine, nimodipine, and nisoldipine.