Passive Ca2+ influx is gradually enhanced by 0.5 to 5m m propranolol in fresh and phosphate ester-depleted human red cells. In fresh cells the active Ca2+ efflux tends to counteract Ca2+ uptake. Membrane hyperpolarization, induced by the K+ transport that accompanies Ca2+ uptake, further enhances the rate of Ca2 uptake. The dissociated, positively charged form of propranolol seems to be crucial in the increase of passive Ca2+ influx caused by the drug. The effect can be attributed to the release of structural Ca2+ from the membrane (lipids). The release of structural Ca2+ promotes the formation of the selectively K+-permeable membrane structure as well. The transitions of lipid structure responsible for the opening of the passive Ca2+ and K+ pathways, however, are not identical. The opening of the K+ pathways is prevented by certain highly lipid-soluble substances (chlorobutanol, heptanol, oligomycin, etc.), whereas the formation of the Ca2+ pathways is unaffected. Passive K+ transport is inhibited by high propranolol concentrations (more intensively at alkaline pH), whereas Ca2+ transport is promoted. A further difference between the passive K+ and Ca2+ pathways is that SH-proteins also seem to be involved in the formation of the K+ pathways, whereas they do not play a specific role in the opening of the passive Ca2+ channels. The additional Ca2+ binding that triggers the formation of the K+ pathways also seems to occur in the protein area of the inner membrane surface.
ASJC Scopus subject areas
- Cell Biology