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

• Published in: Cell calcium (Edinburgh) 2002-05, Vol.31 (5), p.189-200
• Main Authors: Cordero, J F, Romero, P J
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0143-4160
• DOI: 10.1016/S0143-4160(02)00032-5

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.