SUMMARY1. A study has been made of the cellular content and movement of Ca across the membrane of human red blood cells.2. The [Ca] in the cellular contents of fresh red cells is 4 09 x 10-2 mM.The intracellular concentration of free ionic Ca ([Ca2+]) is considered to be less than this value and therefore less than extracellular [Ca2+] under normal conditions.3. Observation of unidirectional Ca fluxes with 45Ca confirms previous reports of low permeability of the red cell membrane for Ca. After nearly 1 week of loading in the cold, intracellular 45Ca content is 1-8 % of extracellular 45Ca content. Appearance in extracellular fluid of 45Ca from coldloaded cells can be considered to arise from two compartments. Efflux of 45Ca from the 'slower compartment' is accelerated by the addition of glucose.4. Starved red cells, incubated at 370 C, after reversible haemolysis for loading with Ca and Mg-ATP, exhibit an outward net transport of Ca against an electrochemical gradient. The transport is associated with the appearance of inorganic phosphate (PI). Cells treated similarly, but without ATP show no transport and no appearance of Pi.5. During the initial phase of transport, 1 3 mole Pi appear per mole Ca transported. 6. The transport of Ca from ATP-loaded cells is highly temperaturedependent, with a Q10 of 3.5.7. Cell membrane adenosine triphosphatase (ATPase) activity of reversibly haemolysed cells is stimulated only by intracellular, and not by extracellular Ca.8. Neither Ca transport in reversibly haemolysed cells, nor the Ca-Mg activated ATPase of isolated cell membranes is sensitive to Na, K, ouabain or oligomycin.

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Active transport of calcium into inside-out vesicles of red blood cell membranes was stimulated equally by (i) the purified protein activator of calcium-activated, magnesium-dependent adenosinetriphosphatase isolated from red cell hemolyzates and (ii) calmodulin, a protein activator of cylic nucleotide phosphodiesterase isolated from bovine brain. The results provide further evidence for the identity of red blood cell activator and calmodulin and show that this cytoplasmic protein may participate in the regulation of plasma membrane calcium transport.

BackgroundAlcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates.MethodsDrowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75.1. The data were narrowed to unintentional drowning, using the ICD-10 external-injury codes V90, V92, and W65–74. Each drowning case had its blood alcohol concentration (BAC) and concentrations of other drugs recorded. Evaluation of the contribution of psychotropic drugs to drowning was based on their blood concentration by means of a 6-grade scale.ResultsAmong victims ≥15 years old, unintentional drownings numbered 1697, of which, 303 (17.9%) were boating-related and 1394 (82.1%) non-boating-related. Among these, 65.0% of boating-related and 61.8% of non-boating-related victims were alcohol-positive (=BAC ≥ 50 mg/dL). The male-to-female ratio in alcohol-positive drownings was 7.3. At least one psychotropic drug appeared in 453 (26.7%) drowning cases, with some victims’ bodies showing up to 7 different drugs. Overall 70 different psychotropic drugs were detectable, with 134 (7.9%) cases both alcohol-negative and psychotropic-drug-positive, of these, 59 (3.5%) were graded 4 to 6, indicating a possible to very probable contribution to drowning. Our findings suggest that psychotropic drugs may play a significant role in drowning, in up to 14.5% of cases, independently or in association with alcohol.ConclusionsPsychotropic drugs alone or in association with alcohol may be an overlooked risk factor in drowning, due to their effects on psychomotor function and cognition. Future studies should also address other mechanisms—for instance drug-induced long-QT syndrome—by which drugs may contribute to drowning.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-017-4306-8) contains supplementary material, which is available to authorized users.

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