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Updated: Jul 18, 2026
Cell-based Calcium Assay for Medium to High Throughput Screening of TRP Channel Functions using FlexStation 3
Published on: August 17, 2011
Pharmacology and drug discovery for T-type calcium channels
1Department of HTS-Molecular Pharmacology, Amgen Inc., Thousand Oaks, California 91320, USA. mcgivern@amgen.com
Abstract:
Voltage-gated calcium channels are found in the plasma membrane of many excitable and non-excitable cells. When open, they permit influx of calcium, which acts as a second messenger to initiate diverse physiological cellular processes. Ten unique alpha1 subunits, grouped in three families (CaV1, CaV2, and CaV3), encode biophysically and pharmacologically distinct low-voltage-activated T-type and high-voltage-activated L-type, N-type, P/Q-type, and R-type calcium channels. T-type calcium channels are found in neurons where they generate low-threshold calcium spikes and influence action potential firing patterns, in heart cells where they influence pacemaking and impulse conduction, in smooth muscle cells where they regulate myogenic tone and proliferation, in endocrine cells where they regulate hormone secretion, and in sperm where they regulate the acrosome reaction. Validation of T-type calcium channels in disease is based on an abundance of data pertaining to clinical efficacy of T-type calcium channel blockers in certain human conditions as well as information relating to the distribution, functional properties, and physiological roles of these channels. This review focuses on the cellular and molecular pharmacology of T-type calcium channels. It describes novel research approaches to discover potent and selective T-type calcium channel modulators as potential drugs for treating human disease and as tools for understanding better the physiological roles of T-type calcium channels.
Insights
T-type calcium channels regulate crucial cellular processes in neurons, heart, and smooth muscle. This review explores their cellular pharmacology and novel drug discovery approaches for human diseases.
Area of Science:
- Cellular and Molecular Pharmacology
- Neuroscience
- Cardiology
Background:
- Voltage-gated calcium channels (VGCCs) are vital for cellular signaling, mediating calcium influx.
- Ten alpha1 subunits form distinct VGCCs, including low-voltage-activated T-type and high-voltage-activated channels.
- T-type calcium channels play key roles in neuronal excitability, cardiac pacemaking, smooth muscle function, and hormone secretion.
Purpose of the Study:
- To review the cellular and molecular pharmacology of T-type calcium channels.
- To highlight novel research approaches for discovering T-type calcium channel modulators.
- To discuss the therapeutic potential of T-type calcium channel modulators for human diseases.
Main Methods:
- Literature review of T-type calcium channel research.
- Analysis of existing data on T-type calcium channel distribution and function.
- Exploration of emerging drug discovery strategies for T-type calcium channel modulators.
Main Results:
- T-type calcium channels are implicated in various physiological processes and diseases.
- Clinical efficacy of T-type calcium channel blockers is established for certain human conditions.
- Novel research approaches are yielding potent and selective T-type calcium channel modulators.
Conclusions:
- T-type calcium channels are critical drug targets for numerous human diseases.
- Understanding T-type calcium channel pharmacology is essential for developing new therapeutics.
- Further research into T-type calcium channel modulators holds promise for treating neurological, cardiovascular, and other disorders.
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