In Stock Cell Lines
The Cacna2d1 Knockout PC-12 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from rat PC-12 pheochromocytoma cells. It features targeted disruption of Cacna2d1, the gene encoding the alpha2delta-1 auxiliary subunit of voltage-gated calcium channels, which interacts with pore-forming subunits such as CaV2.2 and modulates downstream effectors like CaMKII, and serves as the receptor for gabapentinoid drugs. This knockout model attenuates calcium signaling and NGF-induced neurite outgrowth, facilitating studies of channel trafficking, neuropathic pain, and synaptic mechanisms. Applications include calcium imaging, electrophysiology, and drug sensitivity assays for gabapentinoid compounds.
GHITM Knockout Hela Polyclonal Cells
Cat. No. ARG8029
COX19 Knockout Hela Polyclonal Cells
Cat. No. ARG7475
KCTD3 Knockout HGC-27 Polyclonal Cells
Cat. No. ARG30096
ABHD4 Knockout A549 Polyclonal Cells
Cat. No. ARG31031
MEIS1 Knockout 786-O Polyclonal Cells
Cat. No. ARG5131
MYO3B Knockout HEK293T Polyclonal Cells
Cat. No. ARG4499
The Cacna2d1 Knockout PC-12 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from Rattus norvegicus, designed to disrupt the Cacna2d1 gene and ablate expression of the alpha2delta-1 auxiliary calcium channel subunit. This stable loss-of-function model allows precise investigation of voltage-gated calcium channel regulation, trafficking, and downstream signaling without reliance on pharmacological agents. By eliminating alpha2delta-1, it provides a clean experimental system for studying calcium-dependent neuronal functions such as neurite outgrowth and excitability modulation.
The PC-12 host line originates from a rat adrenal pheochromocytoma and is a classical neuroendocrine model for neuronal differentiation. These cells respond to nerve growth factor (NGF) by extending neurites and adopting a sympathetic neuron-like phenotype, making them invaluable for studying neurite outgrowth mechanisms. They express endogenous voltage-gated calcium channels and exhibit robust calcium signaling upon depolarization, rendering them highly suitable for electrophysiological and calcium imaging assays. The PC-12 background is thus ideal for evaluating Cacna2d1 function in a well-characterized excitable cell system.
Cacna2d1 encodes the alpha2delta-1 protein, which associates with pore-forming alpha1 subunits such as CaV1.2 and CaV2.2 to promote channel trafficking and augment calcium currents. This subunit is the target of gabapentinoid drugs gabapentin and pregabalin, which reduce calcium influx. Upstream regulators include NGF, depolarization, and cAMP/CREB signaling, while downstream effectors encompass calmodulin, CaMKII, CREB, and NFAT. Alpha2delta-1 also binds extracellular thrombospondins to facilitate excitatory synaptogenesis. Knockout disrupts these interactions, impairing calcium signal transduction and protein phosphorylation cascades.
In PC-12 cells, Cacna2d1 knockout dramatically reduces NGF-induced neurite outgrowth, linking alpha2delta-1 to growth factor-mediated calcium signaling and transcriptional programs. The knockout line shows diminished depolarization-evoked calcium transients and attenuated activation of CaMKII and CREB, consistent with impaired channel function. This model is relevant for studying neurological disorders such as epilepsy, neuropathic pain, and Brugada syndrome, where alpha2delta-1 dysregulation contributes to pathophysiology. Moreover, it enables direct assessment of gabapentinoid drug specificity and off-target effects.
Researchers can use this cell line in calcium imaging (Fura-2/Fluo-4) to monitor intracellular calcium, patch-clamp electrophysiology for channel biophysics, and neurite outgrowth assays to quantify differentiation. Western blotting for CaV subunits, phospho-CREB/CaMKII analysis, and RT-qPCR of differentiation markers elucidate molecular alterations. Drug sensitivity assays with gabapentin probe pharmacological mechanisms. These complementary approaches allow comprehensive interrogation of alpha2delta-1’s roles in channel regulation, neuronal differentiation, and drug action, facilitating both basic discovery and translational research. For further information, contact Ascent Research.
