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Am J Physiol Renal Physiol (February 5, 2002). doi:10.1152/ajprenal.00239.2001
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Articles in PresS, published online ahead of print February 5, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00239.2001
Submitted on August 1, 2001
Accepted on January 31, 2002

A Mechanogated Nonselective Cation Channel in Proximal Tubule that is ATP-Sensitive

Craig G Hurwitz1, Vivian Y Hu1, and Alan S Segal2*

1 Department of Medicine, University of Vermont, Burlington, VT, USA
2 Department of Medicine, University of Vermont, Burlington, VT, USA; Department of Pharmacology, University of Vermont, Burlington, VT, USA

* To whom correspondence should be addressed. E-mail: asegal{at}zoo.uvm.edu.

Ion channels that are gated in response to membrane deformation or "stretch" are empirically designated stretch-activated (SA) channels. Here we describe a stretch-activated nonselective cation (SA-NSC) channel in the basolateral membrane (BLM) of the proximal tubule (PT) that is nucleotide sensitive. Single channels were studied in cell-intact and cell-free patches from the BLM of PT cells that maintain their epithelial polarity. The limiting inward Cs+ conductance is ~28 pS and channel activity persists following excision into a Ca2+- and ATP-free bath. The stretch dose-response is sigmoidal with half-maximal activation of about -19 mmHg at -40 mV, and the channel is activated by depolarization. The inward conductance sequence is: NH4+ ~ Cs+ ~ Rb+ > K+ ~ Na+ ~ Li+ > Ca2+ ~ Ba2+ > NMDG+ ~ TEA+. The venom of the common Chilean tarantula, Grammostola spatulata, completely blocks channel activity in cell-attached patches. Hypotonic swelling reversibly activates the channel. Intracellular ATP ([ATP]i) reversibly blocks the channel (Ki ~ 0.48 mM), suggesting that channel function is coupled to the metabolic state of the cell. We conclude that this channel may function as a Ca2+ entry pathway and/or be involved in regulation of cell volume. We speculate this channel may be important when [ATP]i is depleted, as occurs during periods of increased transepithelial transport or with ischemic injury.




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Exploring mechanisms involved in renal tubular sensing of mechanical stretch following ureteric obstruction
Am J Physiol Renal Physiol, July 1, 2008; 295(1): F1 - F11.
[Abstract] [Full Text] [PDF]




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