CACNB2 (also known as MYSB; CAVB2; CACNLB2; FLJ23743) encodes a subunit of a voltage-dependent calcium channel protein which is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome which is an autoimmune disorder. Mutations in this gene are associated with Brugada symdrome. Alternatively spliced variants have been identified for this gene.
Five distinct b2 subunits,
varying only in the proximal amino terminus, have been
cloned from different species including rat (Perez-Reyes
et al., 1992 ), rabbit (Hullin et al., 1992 ), human (Rosenfeld
et al., 1993 ), and mouse (Massa et al., 1995 ). Until (2003), however, no more than three of the b2 forms have been identified
in any one species (Qin et al., 1998 ), rendering it ambiguous
whether they represent bona fide splice variants of the b2
gene. (From Takahashi )
A protein complex that forms a transmembrane channel through which calcium ions may pass in response to changes in membrane potential.
The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers.
cacnb2 is the dominant
b subunit expressed in heart (Perez-Reyes et al., 1992 ;
Pichler et al., 1997 ; Haase et al., 2000 ) and retina (Ball et al.,
2002 ), but is also an important component of HVA Ca21
channels expressed in brain (Ludwig et al., 1997 ; Pichler
et al., 1997 ), smooth muscle (Reimer et al., 2000 ), and pancreas (Iwashima et al., 2001 ). (List from Takahashi )
Auxiliary b subunits are potent determinants of Ca2+
channel behavior. Qualitatively, all four b-subunit isoforms
act similarly to markedly increase surface membrane expression of co-expressed alpha1-subunits (Chien et al., 1995 ;
Brice et al., 1997 ; Gao et al., 1999 ; Yamaguchi et al., 2000 ),
dramatically enhance Ca2+ current amplitude over that obtained with alpha1 alone (Singer et al., 1991 ; Jones et al., 1998 ),
and produce hyperpolarizing shifts in the voltage-dependence of channel activation (Singer et al., 1991 ; Perez-Reyes
et al., 1992 ; De Waard et al., 1994 ).
Sequence analysis of the human genome permitted cloning of five Ca2+-channel b2 splice variants (b2a–b2e) that
differed only in their proximal amino-termini. The functional consequences of such b2-subunit diversity were explored in
recombinant L-type channels reconstituted in HEK 293 cells. b2a and b2e targeted autonomously to the plasma membrane,
whereas b2b–b2d localized to the cytosol when expressed in HEK 293 cells. The pattern of modulation of L-type channel
voltage-dependent inactivation gating correlated with the subcellular localization of the component b2 variant—membrane-
bound b2a and b2e subunits conferred slow(er) channel inactivation kinetics and displayed a smaller fraction of channels
recovering from inactivation with fast kinetics, compared to b2b–b2d channels. (Takahashi )