title: Inhibition of the magnesium-sensitive TRPM7-like channel in cardiac myocytes by nonhydrolysable GTP analogs: involvement of phosphoinositide metabolism.
abstract: OBJECTIVE
  A magnesium-inhibited, transient receptor potential melastatin 7 (TRPM7)-like channel is expressed in cardiac cell membranes. The role and regulation of this channel by intracellular nucleotides and membrane components remain unclear.
  
  
  METHODS
  We used the whole-cell voltage-clamp technique in pig isolated ventricular myocytes to investigate the effect of non-hydrolysable guanine nucleotides.
  
  
  RESULTS
  The TRPM7-like current, induced by intracellular dialysis with low [Mg(2+)], remained stable when the intracellular solution contained GTP. Substituting GTP by GTP-gamma-S or Gp-pNp, but not GDP-beta-S, induced a run-down of the current. Under dialysis with GTP-gamma-S, inhibiting phospholipase C by edelfosine or intracellularly adding exogenous phosphatidylinositol-4,5-bisphosphate (PIP(2)) decreased run-down, whereas extracellularly applying carbachol and phenylephrine accelerated it. Pretreatment of cells with pertussis toxin did not prevent the run-down induced by GTP-gamma-S.
  
  
  CONCLUSIONS
  Guanine nucleotides can modulate cardiac TRPM7-like channels via a mechanism linked to G proteins and to PIP(2) metabolism.
authors.affiliation: Department of Cardiovascular Diseases, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Regina
authors.initials: R
authors.lastname: Macianskiene
authors.forename: Asfree
authors.initials: A
authors.lastname: Gwanyanya
authors.forename: Johan
authors.initials: J
authors.lastname: Vereecke
authors.forename: Kanigula
authors.initials: K
authors.lastname: Mubagwa