| First Author | Cang C | Year | 2014 |
| Journal | Nat Chem Biol | Volume | 10 |
| Issue | 6 | Pages | 463-9 |
| PubMed ID | 24776928 | Mgi Jnum | J:306709 |
| Mgi Id | MGI:6718238 | Doi | 10.1038/nchembio.1522 |
| Citation | Cang C, et al. (2014) The voltage-gated sodium channel TPC1 confers endolysosomal excitability. Nat Chem Biol 10(6):463-9 |
| abstractText | The physiological function and molecular regulation of plasma membrane potential have been extensively studied, but how intracellular organelles sense and control membrane potential is not well understood. Using whole-organelle patch clamp recording, we show that endosomes and lysosomes are electrically excitable organelles. In a subpopulation of endolysosomes, a brief electrical stimulus elicits a prolonged membrane potential depolarization spike. The organelles have a previously uncharacterized, depolarization-activated, noninactivating Na(+) channel (lysoNaV). The channel is formed by a two-repeat six-transmembrane-spanning (2x6TM) protein, TPC1, which represents the evolutionary transition between 6TM and 4x6TM voltage-gated channels. Luminal alkalization also opens lysoNaV by markedly shifting the channel's voltage dependence of activation toward hyperpolarization. Thus, TPC1 is a member of a new family of voltage-gated Na(+) channels that senses pH changes and confers electrical excitability to organelles. |
