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Updated: Apr 30, 2026

Patch-Clamp Techniques for Single Endolysosomal Vesicle Analysis
Published on: April 4, 2025
The voltage-gated sodium channel TPC1 confers endolysosomal excitability
Chunlei Cang1, Biruk Bekele1, Dejian Ren1
1Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract:
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 (2×6TM) protein, TPC1, which represents the evolutionary transition between 6TM and 4×6TM 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.
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