Caffeine activates a mechanosensitive Ca(2+) channel in human red cells.
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.
Cordero
J F
JF
Laboratory of Membrane Physiology, Faculty of Sciences, Institute of Experimental Biology, Central University of Venezuela, Aptdo. 47114, Caracas 1041-A, Venezuela.
Romero
P J
PJ
D000255:Adenosine Triphosphate / Q000172:deficiency; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology; D009997:Osmotic Pressure / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013314:Stress, Mechanical
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007038:Hypotonic Solutions; D002110:Caffeine; D000255:Adenosine Triphosphate; D012964:Sodium; D011188:Potassium; D002118:Calcium