A mechanogated nonselective cation channel in proximal tubule that is ATP sensitive.
Ion channels that are gated in response to membrane deformation or "stretch" are empirically designated stretch-activated channels. Here we describe a stretch-activated nonselective cation 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 after 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: NH ~ Cs+ ~ Rb+ > K+ ~ Na+ ~ Li+ > Ca2+ ~ Ba2+ > N-methyl-D-glucamine ~ tetraethylammonium. 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 concentration ([ATP]i) reversibly blocks the channel (inhibitory constant approximately 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.
Hurwitz
Craig G
CG
Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Hu
Vivian Y
VY
Segal
Alan S
AS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000557:Ambystoma; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002412:Cations / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D013111:Spider Venoms / Q000494:pharmacology; D013314:Stress, Mechanical
D002412:Cations; D007473:Ion Channels; D013111:Spider Venoms; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005682:Gadolinium