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Action of Ca2+ agonists/antagonists in mammalian peripheral neurons
E Carbone1, F Clementi, A Formenti
1Dept. Anatomy and Human Physiology, Torino, Milano, Italy.
Abstract:
The action of several ligands on the low- (LVA,T) and high-threshold (HVA,L and N) Ca channels of adult rat sensory neurons and human neuroblastoma IMR32 cells has been investigated. In both cell types, 40 microM Cd2+ and 6.4 microM /omega-Conotoxin (omega-CgTx) selectively blocked the HVA channels, sparing the majority of LVA channels that were antagonized by amiloride and Ni2+. In 50% of the cells, however, /omega-CgTx spared also a 15% of HVA channels that proved to be sensitive to BAY K 8644. The agonistic action of BAY K 8644 on [omega-CgTx-resistant HVA channels caused a large Ba current increase, prolonged current deactivation and acceleration of HVA channels inactivation that was particularly evident in adult rat DRG.
Insights
This study investigated calcium channel activity in rat sensory neurons and human neuroblastoma cells. Specific ligands differentiated between low- (LVA) and high-threshold (HVA) calcium channels, revealing distinct blocking and activating mechanisms.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Calcium channels play crucial roles in neuronal function.
- Distinguishing between low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium channels is essential for understanding cellular excitability.
- Specific ligands are needed to selectively target and study different calcium channel subtypes.
Purpose of the Study:
- To investigate the action of various ligands on LVA and HVA calcium channels.
- To characterize the selectivity of cadmium (Cd2+), omega-conotoxin (omega-CgTx), amiloride, Ni2+, and BAY K 8644 on these channels.
- To elucidate the functional consequences of ligand interactions with HVA channels in specific cell types.
Main Methods:
- Electrophysiological recordings were performed on adult rat sensory neurons and human neuroblastoma IMR32 cells.
- The effects of Cd2+, omega-CgTx, amiloride, Ni2+, and BAY K 8644 on calcium channel currents were analyzed.
- Selective blockade and activation of LVA and HVA channels were assessed.
Main Results:
- Cd2+ and omega-CgTx selectively blocked HVA channels, while amiloride and Ni2+ antagonized LVA channels.
- A subset of HVA channels (15%) in 50% of cells were resistant to omega-CgTx and sensitive to BAY K 8644.
- BAY K 8644 agonism on these resistant HVA channels resulted in increased barium currents, prolonged deactivation, and accelerated inactivation, particularly in rat DRG neurons.
Conclusions:
- Ligands can effectively differentiate between LVA and HVA calcium channel subtypes.
- A distinct subpopulation of HVA channels exhibits unique pharmacological properties.
- These findings contribute to a deeper understanding of calcium channel modulation in neuronal signaling and disease.