Expression of Ca2+ channel subunits during cardiac ontogeny in mice and rats: Identification of fetal α1C and β subunit isoforms

✍ Scribed by Hannelore Haase; Birgit Pfitzmaier; Maureen W. McEnery; Ingo Morano

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 198 KB
• Volume: 76
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(20000315)76:4<695::aid-jcb17>3.0.co;2-q

✦ Synopsis

Functional cardiac L-type calcium channels are composed of the pore-forming ␣ 1C subunit and the regulatory ␤ 2 and ␣ 2 /␦ subunits. To investigate possible developmental changes in calcium channel composition, we examined the temporal expression pattern of ␣ 1C and ␤ 2 subunits during cardiac ontogeny in mice and rats, using sequence-specific antibodies. Fetal and neonatal hearts showed two size forms of ␣ 1C with 250 and 220 kDa. Quantitative immunoblotting revealed that the rat cardiac 250-kDa ␣ 1C subunit increased about 10-fold from fetal days 12-20 and declined during postnatal maturation, while the 220-kDa ␣ 1C decreased to undetectable levels. The expression profile of the 85-kDa ␤ 2 subunit was completely different: ␤ 2 was not detected at fetal day 12, rose in the neonatal stage, and persisted during maturation. Additional ␤ 2 -stained bands of 100 and 90 kDa were detected in fetal and newborn hearts, suggesting the transient expression of ␤ 2 subunit variants. Furthermore, two fetal proteins with ␤ 4 immunoreactivity were identified in rat hearts that declined during prenatal development. In the fetal rat heart, ␤ 4 gene expression was confirmed by RT-PCR. Cardiac and brain ␤ 4 mRNA shared the 3 prime region, predicting identical primary sequences between amino acid residues 62-519, diverging however, at the 5 prime portion. The data indicate differential developmental changes in the expression of Ca 2ϩ channel subunits and suggest a role of fetal ␣ 1C and ␤ isoforms in the assembly of Ca 2ϩ channels in immature cardiomyocytes.