Control of HCO₃-Dependent Exchangers by Cyclic Nucleotides in Vascular Smooth Muscle Cells

A variety of membrane transport systems responsible for the regulation of intracellular pH (pH _i ) have been identified in smooth muscle (Aickin, 1986; Aalkjaer and Cragoe, 1988; Wray, 1988; Kikeri et al., 1990) and smooth muscle-like cells (Boyarsky et al.,1988a,b; Putnam,1990). These include the ubiquitous Na/H exchanger and at least two HC0 ₃ -dependent transport systems (Fig. 1): i) a putative alkalinizing (Na + HCO ₃ )/C1 exchanger (although the role of Cl in this exchanger is still at issue) (Aickin and Brading, 1984; Aalkjaer and Mulvany, 1988); and ii) an acidifying Cl/HCO ₃ exchanger. While these exchangers are important for determining steady state pH _i (Aalkjaer and Cragoe, 1988; Boyarsky et al., 1988a; Wray, 1988; Kikeri et al., 1990; Putnam and Grubbs, 1990), defending pH _i against acid/base disturbances (Aalkjaer and Cragoe, 1988; Boyarsky et al., 1988b; Putnam, 1990) and mediating cellular responses to external signals (Berk et al., 1987; Ganz et al., 1989), only the Na/H exchanger has been extensively studied in regard to the factors which regulate its activity. In fact, the regulation of the HCO ₃ -dependent transport systems is poorly studied in any cell.