STOCHASTIC NATURE AND RED-CELL POPULATION-DISTRIBUTION OF THE SICKLING-INDUCED CA2+ PERMEABILITY

To explore basic properties of the sickling-induced cation permeabilit y pathway, the Ca2+ component (Psickle-Ca) was studied in density-frac tionated sickle cell anemia (SS) discocytes through its effects on the activity of the cells' Ca2+-sensitive K+-channels (K-Ca). The instant state of K-Ca channel activation was monitored during continuous or c yclic deoxygenation of the cells using a novel thiocyanate-dense-cell formation method, Each deoxy pulse caused a reversible, sustained Psic kle-Ca which activated K-Ca channels in only 10-45% of cells at physio logical [Ca2+](0) (''activated cells''), After removal of cells activa ted by each previous deoxy pulse, subsequent pulses generated similar activated cell fractions, indicating a random determination rather tha n the response of a specific vulnerable subpopulation, The fraction of activated cells rose monotonically with [Ca2+](0) along a curve refle cting the cells' distribution of Psickle-Ca, with values high enough i n a small cell fraction to trigger near-maximal K-Ca channels, Consist ent with the stochastic nature of Psickle-Ca, repeated deoxygenated-ox ygenated pulsing led to progressive dense cell formation, whereas sing le long pulses caused one early density shift, Thus deoxygenation-indu ced Ca2+-permeabilization in SS cells is a probabilistic event with la rge cumulative dehydrating potential, The possible molecular nature of Psickle-Ca is discussed.