Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions

Cem Nasuhoglu, Siyi Feng, Yanping Mao, Imman Shammat, Masaya Yamamato, Svetlana Earnest, Mark Lemmon, Donald W. Hilgemann

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Phosphatidylinositol 4,5-bisphosphate (PIP2) affects profoundly several cardiac ion channels and transporters, and studies of PIP2-sensitive currents in excised patches suggest that PIP2 can be synthesized and broken down within 30 s. To test when, and if, total phosphatidylinositol 4-phosphate (PIP) and PIP2 levels actually change in intact heart, we used a new, nonradioactive HPLC method to quantify anionic phospholipids. Total PIP and PIP2 levels (10-30 μmol/kg wet weight) do not change, or even increase, with activation of Gαq/phospholipase C (PLC)-dependent pathways by carbachol (50 μM), phenylephrine (50 μM), and endothelin-1 (0.3 μM). Adenosine (0.2 mM) and phorbol 12-myristate 13-acetate (1μM) both cause 30% reduction of PIP2 in ventricles, suggesting that diacylglycerol (DAG)-dependent mechanisms negatively regulate cardiac PIP2. PIP2, but not PIP, increases reversibly by 30% during electrical stimulation (2 Hz for 5 min) in guinea pig left atria; the increase is blocked by nickel (2 mM). Both PIP and PIP2 increase within 3 min in hypertonic solutions, roughly in proportion to osmolarity, and similar effects occur in multiple cell lines. Inhibitors of several volume-sensitive signaling mechanisms do not affect these responses, suggesting that PIP2 metabolism might be sensitive to membrane tension, per se.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number1 52-1
Publication statusPublished - 2002

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Keywords

  • Cardiac muscle
  • Cell volume
  • Diacylglycerol
  • G protein-coupled receptors
  • Phorbol ester
  • Phosphatidylinositol
  • Phosphatidylinositol 4,5-bisphosphate
  • Phospholipase C

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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