Key result
TWIK1 ion selectivity is modulated by extracellular pH, becoming permeable to sodium at acidic pH and exerting a depolarizing influence on the resting membrane potential in pancreatic beta cells.
TWIK1 ion selectivity is dynamically modulated by extracellular pH, allowing it to act as a background channel whose influence on cell excitability depends on its recycling between acidic endosomes and the plasma membrane.
May alter beta-cell excitability in acidosis; leaves open a role in human islet dysfunction pending validation.
TWIK1 belongs to the family of background K(+) channels with two pore domains. In native and transfected cells, TWIK1 is detected mainly in recycling endosomes. In principal cells in the kidney, TWIK1 gene inactivation leads to the loss of a nonselective cationic conductance, an unexpected effect that was attributed to adaptive regulation of other channels. Here, we show that TWIK1 ion selectivity is modulated by extracellular pH. Although TWIK1 is K(+) selective at neutral pH, it becomes permeable to Na(+) at the acidic pH found in endosomes. Selectivity recovery is slow after restoration of a neutral pH. Such hysteresis makes plausible a role of TWIK1 as a background channel in which selectivity and resulting inhibitory or excitatory influences on cell excitability rely on its recycling rate between internal acidic stores and the plasma membrane. TWIK1(-/-) pancreatic β cells are more polarized than control cells, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.
No takes yet. Share an insight, caveat, or question.
Chatelain et al. (2012) studied this question. Extracellular pH acidification and TWIK1 mutations vs. Neutral pH and wild-type TWIK1 was evaluated on Ion selectivity and channel activity. TWIK1 ion selectivity is modulated by extracellular pH, becoming permeable to sodium at acidic pH and exerting a depolarizing influence on the resting membrane potential in pancreatic beta cells.