P2U purinergic receptor inhibits apical IsK/KvLQT1 channel via protein kinase C in vestibular dark cells

The American Journal of Physiology
D C MarcusM A Scofield

Abstract

Vestibular dark cells (VDC) are known to electrogenically secrete K+ via slowly activating K+ (IsK) channels, consisting of IsK regulatory and KvLQT1 channel subunits, and the associated short-circuit current (Isc) is inhibited by agonists of the apical P2U (P2Y2) receptor (J. Liu, K. Kozakura, and D. C. Marcus. Audit. Neurosci. 2: 331-340, 1995). Measurements of relative K+ flux (JK) with a self-referencing K(+)-selective probe demonstrated a decrease in JK after apical perfusion of 100 microM ATP. On-cell macropatch recordings from gerbil VDC showed a decrease of the IsK channel current (IIsK) by 83 +/- 7% during pipette perfusion of 10 microM ATP. The magnitude of the decrease of Isc by ATP was diminished in the presence of inhibitors of phospholipase C (PLC) and protein kinase C (PKC), U-73122 and GF109203X. Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 20 nM) decreased IIsK by 79 +/- 3% in perforated-patch whole cell recordings, whereas the inactive analog, 4 alpha-PMA, had no effect. In contrast, elevation of cytosolic Ca2+ concentration by A-23187 increased the whole cell IIsK. The expression of the isk gene transcript was confirmed, and the serine responsible for the species-specific response to PKC was fou...Continue Reading

References

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Citations

Aug 24, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·M TeixeiraD Butlen
Dec 21, 2000·American Journal of Physiology. Cell Physiology·P J Smith, J Trimarchi
Jul 18, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Takeshi Yamamoto, Yuichi Suzuki
Jan 31, 2003·American Journal of Physiology. Renal Physiology·Jens Leipziger
Feb 19, 2005·The Journal of Physiology·J E MatosJ Leipziger
Nov 17, 2005·Physiology·Thomas JespersenSøren-Peter Olesen
Jun 13, 2001·American Journal of Physiology. Cell Physiology·D C Marcus, M A Scofield
Feb 8, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Richard Warth, Jacques Barhanin
Aug 3, 2007·American Journal of Physiology. Cell Physiology·Florian LangPhiline Wangemann
Aug 3, 2005·Pflügers Archiv : European journal of physiology·Susanne E HedeIvana Novak
Feb 24, 2001·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·M TeixeiraD Butlen
Feb 15, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Laszlo KölesPeter Illes
Nov 18, 2006·Canadian Journal of Physiology and Pharmacology·Carin WittnichKarim Bandali
Oct 29, 2010·International Journal of Pediatrics·Damian HutterEdgar Jaeggi
May 21, 2014·Journal of Neuroscience Research·Mayumi SakurabaKatsuhisa Ikeda
Jan 5, 2005·Journal of the Society for Gynecologic Investigation·Lubo Zhang
Jun 28, 2000·Journal of the Autonomic Nervous System·G D Housley, P R Thorne
Sep 2, 2003·Biochimica Et Biophysica Acta·Erik M Schwiebert, Akos Zsembery
Nov 4, 2005·Cell Communication and Signaling : CCS·Daniel C MarcusPhiline Wangemann

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