Cloning and expression of a neuronal calcium channel beta subunit.
Although pharmacological and electrophysiological studies have demonstrated the existence of multiple types of voltage-dependent calcium channels in neuronal tissue, the subunit composition of these channels is not well known. Here, we report the cloning and expression of a new rat brain beta subunit (beta 4). Northern blot analysis indicates that beta 4 mRNA is expressed almost exclusively in neuronal tissues, with the highest levels being found in the cerebellum. Coexpression studies indicate that rat beta 4 can interact with rabbit cardiac muscle alpha 1, rabbit skeletal muscle alpha 1, and calcium channels endogenous to Xenopus oocytes. beta 4 modulation of alpha 1 activity is similar to the modulation induced by beta 1, beta 2, or beta 3. The most striking effect of beta subunits is their ability to increase functional alpha 1 activity, which can be measured as either increased dihydropyridine binding to membranes from transfected COS cells or increased calcium channel activity in Xenopus oocytes.
Castellano
A
A
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Wei
X
X
Birnbaumer
L
L
Perez-Reyes
E
E
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D015870:Gene Expression; D007700:Kinetics; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D009865:Oocytes / Q000502:physiology; D011061:Poly A / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014982:Xenopus laevis
D015220:Calcium Channels; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester