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Protoporphyrins modulate voltage-gated Ca current in AtT-20 pituitary cells
D J Linden1, K Narasimhan, D Gurfel
1Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Journal of Neurophysiology
|December 1, 1993
Summary
Zinc-protoporphyrin-IX (ZnPP-IX) inhibits heme-oxygenase-2 (HO-2), reducing calcium currents in pituitary cells. This effect is mediated by superoxide radicals, not cGMP signaling.
Area of Science:
- Neuropharmacology
- Cellular Physiology
Background:
- Heme-oxygenase-2 (HO-2) plays a role in neural tissues.
- Carbon monoxide (CO) production is linked to HO-2 activity.
- Voltage-gated calcium currents are crucial for cellular signaling.
Purpose of the Study:
- To investigate the effect of Zinc-protoporphyrin-IX (ZnPP-IX) on voltage-gated calcium currents in AtT-20 pituitary cells.
- To elucidate the mechanism underlying ZnPP-IX-induced modulation of calcium currents.
Main Methods:
- Whole-cell patch-clamp technique to measure voltage-gated Ca current.
- Extracellular application of ZnPP-IX and related compounds.
- Co-application with superoxide dismutase and cGMP-dependent protein kinase inhibitor.
Main Results:
- ZnPP-IX caused an irreversible, dose-dependent attenuation of Ca current.
- A 5 microM concentration of ZnPP-IX reduced peak current amplitude by 62%.
- The inhibitory effect of ZnPP-IX was blocked by superoxide dismutase, indicating a role for superoxide radicals.
Conclusions:
- ZnPP-IX inhibits voltage-gated Ca currents in pituitary cells.
- The mechanism involves superoxide radical production, not cGMP-dependent pathways.
- HO-2 inhibition by ZnPP-IX impacts calcium signaling in neural tissues.