CaV1.2 | voltage-dependent, L type, alpha 1C subunit calcium channel

Family:
Calcium channels

Subgroups:
L-Type (CaV1.1–CaV1.4), P/Q-Type (CaV2.1), N-Type (CaV2.2), R-Type (CaV2.3), T-Type (CaV3.1–CaV3.3)

Topology:
Six transmembrane alpha helices (S1–S6), total of four homologous domains make up the tetrameric alpha subunit structure

Assembling:
One large alpha subunit forms a functional channel, accessory subunits ( α1, α2δ, β1-4, and γ) are crucial for robust expression, they functionally modulate the alpha subunit

CaV1.2: Background Information

CaV1.2 is a subunit of L-type voltage-dependent calcium channel. In the heart it forms a complex with the subunits β2 and α2δ1 in a 1:1:1 ratio. The alpha-1 consists of 24 transmembrane segments and is the pore forming element through which ions pass into the cell, whereas the β2 and α2δ1 subunits modulate the channel function. CaV1.2 is widely expressed in the smooth muscle, pancreatic cells, fibroblasts, and neurons. However, it is particularly important and well known for its expression in the heart where it mediates L-type currents, which causes calcium-induced calcium release from the ER Stores via ryanodine receptors. It depolarizes at -30 mV and helps define the shape of the action potential in cardiac and smooth muscle. CaV1.2 is inhibited by the action of STIM1.

Gene:
CACNA1C

Human Protein:
UniProt Q13936

Tissue:
Heart, brain, lymphocytes, prostate, bladder, uterus ,stomach, colon, placenta, adrenal gland

Function/ Application:
Ca2+ entry in excitable cells

Pathology:
Arterial hypertension, Long QT syndrome, schizophrenia, Timothy syndrome, BRGDA3, bipolar disorder, schizophrenia

Interaction:
Kir/Gem, CSN5/Jab1, β1-4 subunits, α2δ subunits, NF-κB, osteoprotegerin

Modulator:
Verapamil, nifedipine, kurtoxin, calcicludine, mibefradil, calciseptine, BAYK-8644, verapamil

Assays:
Patch Clamp: whole cell, room temperature

Particularities:
CaV channels often show a rundown phenomenon. Adequate intra- and extrcellular solutions are essential for a good data quality.

Recommended Reviews:
Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacol Rev. 57 (4): 411–25.

Data and Applications

CaV1.2 - Stable recording from frozen stock cells

icon sp96   170922 CaV1.2 Data SyncroPatch384PESyncroPatch 384PE data and applications:
Cells were kindly provided by Charles River.

Screenshots of the PatchControl 384 software showing hCaV1.2β2/α2δ1 current traces in response to a voltage step protocol and the corresponing current-voltage relationship plot. Measured on the SyncroPatch 384PE using perforated patch methodology (Escin) and multi-hole chips (4 holes per well), the success rate of valuable data for the analysis was 100 %. The cells were used from a frozen cell stock (after induction) and recorded stably for more than 20 minutes. The IC50 value of Nifedipine was determined as 21 nM.

CaV1.2 - Current Voltage Relationship

Cav12 IV

icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

Shown are raw current traces (top) and the constructed peak current-voltage relationship (bottom) of CaV1.2 (HEK293) recorded on the SyncroPatch 96.

 

 

 

 

 

Cardiomyocytes (Ventricular Myocytes) - Recordings

VentricularMyocyte1

icon pap   Port-a-Patch data and applicatons:
Thanks to S. Rakovic and D. Terrar from University of Oxford, for preparing the cardiomyocytes used in these experiments.

Ca2+ current recorded from a ventricular myocyte. Raw current voltage relationship and peak current data are plotted (top). From the IV-plot the half-activating voltage was determined as -16 mV. The current was later blocked by the L-type Ca2+ channel blocker, nifedepine (10 µM). Currents were elicited by stepping to +10 mV for 200 ms from a holding potential of -40 mV every 5 seconds.

Application Notes

CaV1.2 - "Stability and Pharmacology of CaV1.2 Channels on Nanion’s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (5.3 MB)
Cells were kidly provided by Charles River.

CaV1.2 - "High Throughput Pharmacology of CaV1.2 Channels on Nanion’s SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note:   logo pdf   (2.7 MB)
Cells were kindly provided by SB Drug Discovery.  

Cardiomyocytes - "Impedance and EFP recordings of Pluricyte Cardiomyocytes on the CardioExcyte 96"

Icon CE   CardioExcyte 96 Application Note   logo pdf   (1.4 MB)
Cells were kindly provided by Pluriomics.

Cardiomyocytes - "Impedance and EFP recordings of Cor.4U cells using Nanion’s CardioExcyte 96"

Icon CE   CardioExcyte 96 Application Note   logo pdf   (1.5 MB)
Cells were kindly provided by Axiogenesis.  

Cardiomyocytes - "Combining automated patch clamp, impedance and EFP of hiPSC-CMs"

Icon CE   CardioExcyte 96   icon sp96   SyncroPatch 3984PE   icon pl   Patchliner Application Note 
Cells kindly provided by Takara-Clonetech.

Cardiac Ion Channels - "Simultaneous Assessment of CiPA Stipulated Ion Channels on the SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (1.3 MB)
Cells were kindly provided by Charles River.

Cardiac Ion Channels - "High Throughput Screening of Cardiac Ion Channels"

icon sp96   SyncroPatch 384PE   icon pl   Patchliner   Icon CE   CardioExcyte 96 application note   logo pdf   (0.2 MB)

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