Related Experiment Video

Updated: May 27, 2026

Combining Optogenetics with Artificial microRNAs to Characterize the Effects of Gene Knockdown on Presynaptic Function within Intact Neuronal Circuits
09:17

Combining Optogenetics with Artificial microRNAs to Characterize the Effects of Gene Knockdown on Presynaptic Function within Intact Neuronal Circuits

Published on: March 14, 2018

Roscovitine inhibits CaV3.1 (T-type) channels by preferentially affecting closed-state inactivation

Viktor Yarotskyy1, Keith S Elmslie

  • 1Department of Pharmacology and Physiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. viktor_yarotskyy@urmc.rochester.edu

The Journal of Pharmacology and Experimental Therapeutics
|November 18, 2011
PubMed

Insights

Roscovitine, an anticancer drug, inhibits T-type calcium channels (Ca(V)3.1) by stabilizing their closed-inactivated state. This dual action on cyclin-dependent kinases and Ca(V)3.1 channels may enhance its anticancer efficacy.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • T-type calcium channels (Ca(V)3) are implicated in cancer development.
  • Ca(V)3 channel blockers are explored as potential anti-cancer therapeutics.
  • Roscovitine, a cyclin-dependent kinase (CDK) inhibitor, affects ion channel activity.

Purpose of the Study:

  • To investigate the effect of roscovitine on Ca(V)3.1 channels.
  • To determine the mechanism by which roscovitine inhibits Ca(V)3.1 channel activity.
  • To assess the potential of roscovitine's dual inhibitory action in cancer treatment.

Main Methods:

  • Transient expression of Ca(V)3.1 channels in human embryonic kidney 293 cells.
  • Whole-cell patch-clamp technique to record ionic currents.
  • Analysis of voltage dependence, inactivation, and deactivation kinetics.

Main Results:

  • Roscovitine blocks Ca(V)3.1 channels with an EC₅₀ of 10 μM, showing higher affinity in depolarized cells.
  • Roscovitine shifts the voltage dependence of closed-state inactivation negatively.
  • Inhibition is primarily due to accelerated closed-state inactivation and slowed recovery from inactivation, with minor effects on deactivation and open-state inactivation.

Conclusions:

  • Roscovitine inhibits Ca(V)3.1 channels within its therapeutic range (10-50 μM).
  • The mechanism involves stabilization of the closed-inactivated state of Ca(V)3.1 channels.
  • Roscovitine's combined inhibition of CDKs and Ca(V)3.1 channels may contribute to its anti-cancer properties.

More Related Videos

Measuring Fast Calcium Fluxes in Cardiomyocytes12:10

Measuring Fast Calcium Fluxes in Cardiomyocytes

Published on: November 29, 2011

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine06:40

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine

Published on: April 23, 2020

Related Concept Videos

Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
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 types of...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
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 types of...