| First Author | Singh H | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 26 | Pages | 10836-41 |
| PubMed ID | 23754429 | Mgi Jnum | J:197971 |
| Mgi Id | MGI:5495047 | Doi | 10.1073/pnas.1302028110 |
| Citation | Singh H, et al. (2013) mitoBKCa is encoded by the Kcnma1 gene, and a splicing sequence defines its mitochondrial location. Proc Natl Acad Sci U S A 110(26):10836-41 |
| abstractText | The large-conductance Ca(2+)- and voltage-activated K(+) channel (BKCa, MaxiK), which is encoded by the Kcnma1 gene, is generally expressed at the plasma membrane of excitable and nonexcitable cells. However, in adult cardiomyocytes, a BKCa-like channel activity has been reported in the mitochondria but not at the plasma membrane. The putative opening of this channel with the BKCa agonist, NS1619, protects the heart from ischemic insult. However, the molecular origin of mitochondrial BKCa (mitoBKCa) is unknown because its linkage to Kcnma1 has been questioned on biochemical and molecular grounds. Here, we unequivocally demonstrate that the molecular correlate of mitoBKCa is the Kcnma1 gene, which produces a protein that migrates at approximately 140 kDa and arranges in clusters of approximately 50 nm in purified mitochondria. Physiological experiments further support the origin of mitoBKCa as a Kcnma1 product because NS1619-mediated cardioprotection was absent in Kcnma1 knockout mice. Finally, BKCa transcript analysis and expression in adult cardiomyocytes led to the discovery of a 50-aa C-terminal splice insert as essential for the mitochondrial targeting of mitoBKCa. |
