Functional Embryonic Cardiomyocytes after Disruption of the L-type α1C (Ca 1.2) Calcium Channel Gene in the Mouse

Seisenberger, Claudia; Specht, Verena; Welling, Andrea; Platzer, Josef; Pfeifer, Alexander; Kühbandner, Susanne; Striessnig, Jörg; Klugbauer, Norbert; Feil, Robert; Hofmann, Franz

doi:10.1074/jbc.m006467200

Cited by 255 publications

(219 citation statements)

References 36 publications

Supporting

Mentioning

209

Contrasting

Order By: Relevance

“…In mice, global knockout of Cacna1c (which encodes Ca v 1.2) is lethal [4], whereas beta cell-specific disruption has demonstrated that Ca v 1.2 is critical for insulin release [5,6], especially during the first phase [7]. Ca v 1.3, on the other hand, has been proposed to play a central role during murine postnatal beta cell generation and proliferation [8], but is also differentially regulated in a diabetogenic diet mouse model [9].…”

Section: Introductionmentioning

confidence: 99%

The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes

et al. 2012

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes

et al. 2012

View full text Add to dashboard Cite

show abstract

“…For the major calcium transporters, significant defects are lethal in embryonic life, such as in the Cav1.2 L-type calcium channel [Seisenberger et al, 2000]. Interestingly, for the closely related Cav1.2 and Cav1.3 L-type calcium channels, which are likely to be the principal calcium channels in stretch-related calcium fluxes in osteoblasts, the Cav1.3 channel may partially compensate for loss of function of Cav1.2 [Xu et al, 2003].…”

Section: Calcium-dependent Cellular Regulation In the Osteoblast And mentioning

confidence: 99%

Calcium Signalling and Calcium Transport in Bone Disease

Blair

Schlesinger

Huang

et al.

Subcellular Biochemistry

View full text Add to dashboard Cite

Calcium transport and calcium signalling mechanisms in bone cells have, in many cases, been discovered by study of diseases with disordered bone metabolism. Calcium matrix deposition is driven primarily by phosphate production, and disorders in bone deposition include abnormalities in membrane phosphate transport such as in chondrocalcinosis, and defects in phosphate-producing enzymes such as in hypophosphatasia. Matrix removal is driven by acidification, which dissolves the mineral. Disorders in calcium removal from bone matrix by osteoclasts cause osteopetrosis. On the other hand, although bone is central to management of extracellular calcium, bone is not a major calcium sensing organ, although calcium sensing proteins are expressed in both osteoblasts and osteoclasts. Intracellular calcium signals are involved in secondary control including cellular motility and survival, but the relationship of these findings to specific diseases is not clear. Intracellular calcium signals may regulate the balance of cell survival versus proliferation or anabolic functional response as part of signalling cascades that integrate the response to primary signals via cell stretch, estrogen, tyrosine kinase, and tumor necrosis factor receptors Keywords Hypophosphatasia; chondrocalcinosis; osteopetrosis; osteoporosis Although bone is not considered a major calcium sensing organ in humans, the cells of bone tissue control over 99% of the human body's calcium content. The principal calcium sensors that regulate bone calcium uptake and release are in the parathyroid glands. Bone function is also modified by vitamin D and by calcium transport in the kidney and intestine. These indirect mechanisms of controlling bone calcium metabolism are beyond the scope of our considerations here. In spite of processing such massive quantities of the Ca 2+ bone cells use calcium in their homeostatic control processes. The massive movement of calcium is carried out by specialized and regulated transporters. Defects in the transporters cause diseases with affect bone structure or function. Indeed, inborn errors have been very important in defining the calcium transport mechanisms in bone.Additionally, calcium is used by bone forming and bone degrading cells as a secondary mediator of hormone and cytokine action. These actions include roles in intercellular communication within groups of osteoblasts, which are connected by gap junctions [Henriksen et al., 2006]. These osteoblast groups function in a coordinated fashion in bone synthesis and maintenance, and are collectively known as the osteon. Osteoblasts in these groups are connected by gap junctions which are capable of propagating signals in the cell groups, including calcium waves [Xia and Ferrier, 1992]. Calcium is also an important regulator of

show abstract

“…Ca V 1.2 α 1C ( CACNA1C ) plays a critical role in the cardiovascular function. Deletion of α 1C subunit in mice resulted in embryonic lethality [11], and conditional knockout of smooth muscle α 1C (SMAKO) lowered the arterial blood pressure in mice [12]. Recently, multiply alternative splicing events have been found in CACNA1C , which optimize the functions of Ca V 1.2 channel [13,14].…”

Section: Molecular Basis Of L-type Calcium Channelmentioning

confidence: 99%

Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia

et al. 2018

View full text Add to dashboard Cite

The voltage-gated L-type calcium channel (LTCC) is essential for multiple cellular processes. In the heart, calcium influx through LTCC plays an important role in cardiac electrical excitation. Mutations in LTCC genes, including CACNA1C, CACNA1D, CACNB2 and CACNA2D, will induce the dysfunctions of calcium channels, which result in the abnormal excitations of cardiomyocytes, and finally lead to cardiac arrhythmias. Nevertheless, the newly found mutations in LTCC and their functions are continuously being elucidated. This review summarizes recent findings on the mutations of LTCC, which are associated with long QT syndromes, Timothy syndromes, Brugada syndromes, short QT syndromes, and some other cardiac arrhythmias. Indeed, we describe the gain/loss-of-functions of these mutations in LTCC, which can give an explanation for the phenotypes of cardiac arrhythmias. Moreover, we present several challenges in the field at present, and propose some diagnostic or therapeutic approaches to these mutation-associated cardiac diseases in the future.

show abstract

Functional Embryonic Cardiomyocytes after Disruption of the L-type α1C (Ca 1.2) Calcium Channel Gene in the Mouse

Cited by 255 publications

References 36 publications

The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes

The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes

Calcium Signalling and Calcium Transport in Bone Disease

Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia

Contact Info

Product

Resources

About