Related Experiment Video
Updated: Aug 10, 2025
Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes
Published on: January 10, 2011
Voltage-Gated T-Type Calcium Channel Modulation by Kinases and Phosphatases: The Old Ones, the New Ones, and the
Ankush Sharma1, Ghazala Rahman1, Julia Gorelik2
1Department of Biotechnology, Indian Institute of Technology Hyderabad (IITH), Kandi 502284, Telangana, India.
Abstract:
Calcium (Ca2+) can regulate a wide variety of cellular fates, such as proliferation, apoptosis, and autophagy. More importantly, changes in the intracellular Ca2+ level can modulate signaling pathways that control a broad range of physiological as well as pathological cellular events, including those important to cellular excitability, cell cycle, gene-transcription, contraction, cancer progression, etc. Not only intracellular Ca2+ level but the distribution of Ca2+ in the intracellular compartments is also a highly regulated process. For this Ca2+ homeostasis, numerous Ca2+ chelating, storage, and transport mechanisms are required. There are also specialized proteins that are responsible for buffering and transport of Ca2+. T-type Ca2+ channels (TTCCs) are one of those specialized proteins which play a key role in the signal transduction of many excitable and non-excitable cell types. TTCCs are low-voltage activated channels that belong to the family of voltage-gated Ca2+ channels. Over decades, multiple kinases and phosphatases have been shown to modulate the activity of TTCCs, thus playing an indirect role in maintaining cellular physiology. In this review, we provide information on the kinase and phosphatase modulation of TTCC isoforms Cav3.1, Cav3.2, and Cav3.3, which are mostly described for roles unrelated to cellular excitability. We also describe possible potential modulations that are yet to be explored. For example, both mitogen-activated protein kinase and citron kinase show affinity for different TTCC isoforms; however, the effect of such interaction on TTCC current/kinetics has not been studied yet.
Insights
Calcium ions (Ca2+) regulate cell functions, with T-type Ca2+ channels (TTCCs) crucial for signal transduction. Kinases and phosphatases modulate TTCCs, impacting cellular physiology and potentially new therapeutic targets.
Area of Science:
- Cellular Biology
- Molecular Physiology
- Ion Channel Research
Background:
- Intracellular calcium (Ca2+) levels are critical regulators of diverse cellular processes, including proliferation, apoptosis, and gene transcription.
- Maintaining calcium homeostasis involves complex buffering, storage, and transport mechanisms, with specialized proteins playing key roles.
- T-type Ca2+ channels (TTCCs), a family of low-voltage-activated channels, are vital for signal transduction in both excitable and non-excitable cells.
Purpose of the Study:
- To review the known kinase and phosphatase modulation of TTCC isoforms (Cav3.1, Cav3.2, Cav3.3).
- To explore potential, yet uninvestigated, modulations of TTCCs by other signaling pathways.
- To highlight the broader physiological and pathological implications of TTCC regulation beyond cellular excitability.
Main Methods:
- Literature review of existing studies on TTCCs and their regulation by kinases and phosphatases.
- Analysis of research identifying interactions between specific kinases (e.g., MAP kinase, citron kinase) and TTCC isoforms.
- Identification of research gaps concerning the functional consequences of these interactions.
Main Results:
- Kinases and phosphatases are established modulators of TTCC activity, influencing cellular physiology.
- Specific kinases, such as mitogen-activated protein kinase and citron kinase, exhibit affinity for certain TTCC isoforms.
- The functional impact of these kinase-TTCC interactions on channel kinetics and currents remains largely uncharacterized.
Conclusions:
- Kinase and phosphatase regulation of TTCCs is a significant mechanism influencing cellular functions.
- Further research is needed to elucidate the functional consequences of interactions between TTCCs and kinases like MAP kinase and citron kinase.
- Understanding these regulatory pathways may reveal novel therapeutic strategies for diseases involving TTCC dysfunction.
Related Concept Videos
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:19The Role of Ion Channels in Neuronal Computation
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
01:26Voltage-gated Ion Channels
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
01:27Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
01:12Mechanically-gated Ion Channels