CRITICAL ROLE OF BICARBONATE IN CALCIUM RELEASE FROM BONE

Calcium release from cultured bone is pH dependent; net Calcium flux (J(Ca)) from bone increases with decreasing pH. At a similar decrement in pH there is greater J(Ca) when acidosis is produced by a low medium bicarbonate concentration ([HCO3-]), a model of metabolic acidosis (Met), compared with an increased medium PCO2, a model of respiratory acidosis (Resp). To separate the role of [HCO3-] from that of pH in inducing J(Ca) we cultured calvariae for 3 h under three different neutral (pH almost-equal-to 7.4) isohydric environments [control (Ctl), fully compensated Met (C-Met), or fully compensated Resp (C-Resp)] and two different acid (pH almost-equal-to 7.1) isohydric environments (Met or Resp). During neutral pH (Ctl, C-Met, and C-Resp) there was J(Ca) from bone during C-Met (decreased [HCO3-]), no net flux during Ctl (normal [HCO-3]), and J(Ca) into bone during C-Resp (increased [HCO3-]); and J(Ca) was correlated inversely with [HCO3-] (r = -0.824, n = 36, P < 0.001). During acid pH there was greater J(Ca) from bone during Met (decreased [HCO3-]) than during Resp (normal [HCO3-]); and J(Ca) was again correlated inversely with [HCO3-] (r = -0.848, n = 22, P < 0.001). J(Ca) from bone during Met and Resp was greater than C-Met and C-Resp, respectively. The addition of the osteoclastic inhibitor salmon calcitonin did not alter the relative J(Ca) results. Thus at a constant pH the magnitude of J(Ca) from cultured neonatal mouse calvariae appears dependent on the [HCO3-]; the lower the [HCO3-], the greater the calcium efflux. However, at a constant [HCO3-], calcium flux is pH dependent; the lower the pH, the greater the calcium efflux.