Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions.
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 PIP(2) levels actually change in intact heart, we used a new, nonradioactive HPLC method to quantify anionic phospholipids. Total PIP and PIP2 levels (10-30 micromol/kg wet weight) do not change, or even increase, with activation of Galpha(q)/phospholipase C (PLC)-dependent pathways by carbachol (50 microM), phenylephrine (50 microM), and endothelin-1 (0.3 microM). Adenosine (0.2 mM) and phorbol 12-myristate 13-acetate (1microM) 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.
Nasuhoglu
Cem
C
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA.
Feng
Siyi
S
Mao
Yanping
Y
Shammat
Imman
I
Yamamato
Masaya
M
Earnest
Svetlana
S
Lemmon
Mark
M
Hilgemann
Donald W
DW
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D004553:Electric Conductivity; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria; D006352:Heart Ventricles; D006728:Hormones / Q000502:physiology*; D006982:Hypertonic Solutions / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism* / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D006728:Hormones; D006982:Hypertonic Solutions; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate