Permeation as a Cation

Cadmium accumulation by MDCK cells also appears to be mediated in part by agonist-stimulated calcium channels (Flanagan and Friedman 1991). Parathyroid hormone, a stimulator of calcium uptake in MDCK cells, increased cadmium uptake. The dihydropyridine agonist BAY K8644 augmented the effect of parathyroid hormone, an effect that was competitively inhibited by the calcium channel antagonist nifedipine (Flanagan and Friedman 1991). 

Simons and Pocock (1987) obtained similar results in a study of lead uptake by adrenal medullary cells. They found that metal influx was stimulated by depolarizing the cells in high external K, but that the stimulated influx was blocked by methoxyverapamil (D600) with an affinity that was higher than that for blockade of Ca influx (0.4 vs. 4.7//M). Lead uptake was stimulated by the calcium channel agonist BAY-K8644. As was seen with cadmium, these results are consistent with the notion that voltage-dependent calcium channels could be an important route for the entry of lead into cells. Pb permeation was not affected if Cl was replaced by NO, an observation consistent with the relatively low affinity of Pb for 

Cl complexation (Butler 1964). Tomsig and Suszkiw (1990) used fura2 as a probe for lead entry into chromaffin cells and found that, once inside the cell, the lead was effective in releasing norepinephrine at concentrations three orders of magnitude lower than that required for calcium-induced exocytosis. 

Cd and Mn may also be substrates for ion efflux mechanisms such as the Na-Ca exchanger (Frame and Milanick 1991). It has long been appreciated that a number of metals, and in particular and Mn , inhibit this exchanger (Philipson 1985). Recent studies by Frame and Milanick (1991) demonstrate that this inhibition is competitive, and that these metals are in fact transported as substitutes for Ca. The for Ca, Cd , and Mn uptake by ferret red blood cells is roughly similar, —10//M, as is the (Frame and Milanick 1991), indicating that the transport properties of cadmium and manganese are similar to those of calcium in this system. 

Zinc efflux from human red blood cells may also involve a Ca exchange mechanism (Simons 1991), but the transport system involved is not well characterized. Zn release from human erythrocytes is stimulated by extracellular Ca , but is unaffected by ouabain, 4,4 -diisothiocyano-2,2 -stilbene disulfonate (DIDS), or cytochalasin B, suggesting that a Zn-Ca exchanger mediates zinc efflux in these cells. 

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