Disease relevance of Cacna1e

• Arrhythmia in isolated prenatal hearts after ablation of the Cav2.3 (alpha1E) subunit of voltage-gated Ca2+ channels [1].
• Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(v)2.3 (alpha 1E) subunit of voltage-gated Ca(2+) channels [2].
• Transcripts of alpha1A, alpha1B, alpha1E, alpha1F, alpha1H, beta3, and beta4 subunits were detected by polymerase-chain reaction (PCR) in the dorsal root ganglion, suggesting the existence of a variety of voltage-dependent Ca2+ channels [3].
• Delayed-type hypersensitivity responses differed from IgG responses, i.e., BXI elicited responses to alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II); BII, to alpha 3(XI) and alpha 1(II) exclusively [4].
• Neuroendocrine cells in vitro (beta TC3 insulinoma cells and AtT-20 pituitary cell lines) expressed predominantly one alpha 1E isoform [5].

High impact information on Cacna1e

• A phylogenetic tree representing evolutionary relationships indicates that BIII is grouped together with the other rabbit brain calcium channels, BI and BII, into a subfamily that is distinct from the dihydropyridine-sensitive L-type subfamily [6].
• Here we generated alpha1E-deficient mice (alpha1E-/-) and examined the status of voltage-sensitive Ca2+ currents in central amygdala (CeA) neurons that exhibit abundant alpha1E expression and R-type Ca2+ currents [7].
• Coexpression of alpha2delta-3 with alpha1C and cardiac beta2a or alpha1E and beta3 subunits shifted the voltage dependence of channel activation and inactivation in a hyperpolarizing direction and accelerated the kinetics of current inactivation [8].
• Expression of human alpha 1E in HEK293 cells and Xenopus oocytes produced high voltage-activated Ca2+ currents that inactivated rapidly (tau approximately 20 ms at 0 mV) [9].
• We observed that these alpha 1E transcripts were widely distributed in the central nervous system [9].

Biological context of Cacna1e

• Cloning of 5'-flanking region and a polymorphic CTT trinucleotide repeat within 5'-untranslated region of mouse R-type calcium channel alpha1-subunit (Cchra1) gene, and its genetic mapping [10].
• To know the function of the Ca2+ channel containing alpha(1)2.3 (alpha1E) subunit (Ca(v)2.3 channel) in spermatozoa, we analyzed Ca2+ transients and sperm motility using a mouse strain lacking Ca(v)2.3 channel [11].
• Using this polymorphism, the Cchra1 was mapped to the region of chromosome 1 where the synteny to human chromosome 1q was conserved [10].
• While fragments of a new rat alpha1E isoform are amplified from the 5'-end, three known fragments of the II/III-loop and two known isoforms homologue to the 3'-coding region are detected, which in the last case are discriminated by a 129 base pair insertion [12].

Anatomical context of Cacna1e

• In the cerebellar cortex anterior lobe, Cav2.3 staining was predominantly somatodendritic; whilst in the posterior lobe, perisomatic staining was seen primarily [13].
• Compensatory contribution of Cav2.3 channels to acetylcholine release at the neuromuscular junction of tottering mice [14].
• Localization of the calcium channel subunits Cav1.2 (alpha1C) and Cav2.3 (alpha1E) in the mouse organ of Corti [15].
• Around P14, Cav2.3 immunoreactivity disappeared from these structures and from P19 onwards it was observed in the basal poles of the outer hair cell membranes [15].
• These latter findings imply a possible role of alpha1E-based R-type Ca2+ currents in amygdala physiology associated with fear [7].

Associations of Cacna1e with chemical compounds

• However, electrophysiological data was not consistent with a role for the Cav2.3 subunit in mediating presynaptic GABA release [13].
• Anesthetic sensitivities to propofol and halothane in mice lacking the R-type (Cav2.3) Ca2+ channel [16].
• Interestingly 200 microM NA was basically unable to inhibit alpha1E Ca(2+) channels expressed in Xenopus oocytes, questioning that this alpha subunit codes for the T-type Ca(2+) channels present in spermatogenic cells [17].

Other interactions of Cacna1e

• Probably, there is a small reduction in functional presynaptic Cav2.1 channels at Tg NMJs, which is compensated for by Cav2.3 channels [14].
• The immunohistochemical localization of Cav1.2 (alpha1C) and Cav2.3 (alpha1E) Ca2+ channels was studied in the developing and adult mouse organ of Corti using subunit-specific antibodies and fluorescent secondary antibodies with cochlear cryosections [15].

Analytical, diagnostic and therapeutic context of Cacna1e

• Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine tolerance [18].
• To identify the members of the voltage-dependent Ca2+ channel family possibly present in sperm, we have looked for the expression of the alpha 1A, alpha 1B, alpha 1C, alpha 1D and alpha 1E genes in mouse testis and in purified spermatogenic cell populations with RT-PCR [19].
• Western blot analysis demonstrated significant alpha1C protein subunit expression, with less alpha1D subunit apparent, while alpha1A, alpha1B and alpha1E subunit expression was undetectable [20].
• For the II-III loop three different alpha1E cDNA fragments are amplified from mouse and human brain, showing that isoforms originally predicted from sequence alignment of different species are expressed in a single one [21].

References