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Physiopathology of neuronal voltage-operated calcium channels
E Sher1, E Biancardi, M Passafaro
1CNR Center of Cytopharmacology, University of Milan, Italy.
Abstract:
Voltage-operated calcium channels are multimeric transmembrane proteins crucially involved in control of calcium homeostasis. Multiple types of voltage-operated calcium channels have been described in both the nervous system and peripheral tissues. Different channels can be classified according to either their biophysical properties or their pharmacology, biochemical and molecular structure, and localization and functional role. Concentrating on neuronal cells, this paper reviews the different properties of low- and high-voltage activated channels, as well as various attempts to subdivide high-voltage activated channels into different subtypes (L, N, omega, P, etc.). The availability of selective drugs (such as dihydropyridines) and natural toxins (such as omega-Conotoxin, omega-agatoxin, and funnel-web spider toxins), which bind to specific channel subtypes, has greatly helped in channel classification. The emerging view is that there are many members of the family of voltage-operated calcium channels, each with its own molecular structure, a different pharmacology, a different localization, and possibly a different physiological role. Different calcium subtypes are selectively affected in human and animal diseases. The use of omega-Conotoxin has led to identification of the channel subtype (omega) specifically affected in Lambert-Eaton myasthenic syndrome (a human disease of neurotransmission), and has permitted development of new diagnostic approaches to the disease.
Insights
Voltage-operated calcium channels control calcium levels and have diverse subtypes. Selective drugs and toxins aid in classifying these neuronal channels and understanding diseases like Lambert-Eaton myasthenic syndrome.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Voltage-operated calcium channels (VOCCs) are critical transmembrane proteins for calcium homeostasis.
- Multiple VOCC types exist in nervous and peripheral systems, classified by biophysical, molecular, and functional properties.
Purpose of the Study:
- To review the properties of low- and high-voltage activated calcium channels in neuronal cells.
- To discuss the classification of high-voltage activated channels into subtypes (L, N, omega, P, etc.).
Main Methods:
- Review of scientific literature on VOCCs.
- Analysis of classification strategies based on biophysical properties, molecular structure, and pharmacology.
- Examination of the role of selective drugs and toxins in channel identification.
Main Results:
- VOCCs exhibit diverse properties, with distinct subtypes identified.
- Selective drugs (e.g., dihydropyridines) and toxins (e.g., omega-Conotoxin) are crucial for classifying VOCC subtypes.
- Specific VOCC subtypes are implicated in human and animal diseases.
Conclusions:
- A growing understanding reveals numerous VOCC family members, each with unique structures, pharmacology, localization, and physiological roles.
- Omega-Conotoxin facilitated the identification of the specific channel subtype in Lambert-Eaton myasthenic syndrome.
- This research supports the development of novel diagnostic methods for VOCC-related diseases.