Caffeine activates a mechanosensitive Ca(2+) channel in human red cells

Cell Calcium. 2002 May;31(5):189-200. doi: 10.1016/S0143-4160(02)00032-5.

Abstract

Caffeine is known to activate influx of both mono- and divalent cations in various cell types, suggesting that this xanthine opens non-selective cation channels at the plasma membrane. This possibility was investigated in human erythrocytes, studying the caffeine action on net Ca(2+), Na(+) and K(+) movements in ATP-depleted cells. Whole populations and subpopulations of young and old erythrocytes were employed. Caffeine was tested in the presence of known mechanosensitive channel blockers (Gd(3+), neomycin and amiloride) and ruthenium red as a possible inhibitor. Caffeine enhanced net cation fluxes in a concentration-dependent way. In whole populations, the Ca(2+) entry elicited by 20 mM caffeine was fully suppressed by Gd(3+) (5 microM), amiloride (250 microM) and ruthenium red (100 microM) and partially blocked by neomycin (100 microM). The above blockers also inhibited caffeine-dependent Na(+) entry whilst showing antagonistic effects on the corresponding K(+) efflux. These compounds fully suppressed hypotonically-induced (-35 mOsm/kg) Ca(2+) influx at nearly the same concentrations completely blocking caffeine-stimulated Ca(2+) entry. The effect of inhibitors on Ca(2+) influx in young cells exceeded that in old cells at similar concentrations. The results clearly show that caffeine stimulates a stretch-activated Ca(2+) channel in human red cells and that aged cells are less susceptible to mechanosensitive channel blockers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / deficiency
  • Caffeine / pharmacology*
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Cellular Senescence / physiology
  • Dose-Response Relationship, Drug
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Humans
  • Hypotonic Solutions / pharmacology
  • Osmotic Pressure / drug effects
  • Potassium / metabolism
  • Sodium / metabolism
  • Stress, Mechanical

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Hypotonic Solutions
  • Caffeine
  • Adenosine Triphosphate
  • Sodium
  • Potassium
  • Calcium