Regulation of gap junctions in vascular smooth muscle.

Abstract

Gap junctions form low resistance pathways between neighboring cells and thereby provide for coordination of tissue function. In vascular smooth muscle these channels are believed to be important in maintenance of and coordination of changes in vessel tone. In this study we demonstrate that vascular smooth muscle cells from vessels of different origin and species differ in the connexin protein expressed as well as in the size of the channel formed by these proteins. We have shown that pig coronary and rat mesentery express mRNA for Cx43 and exhibit a single channel conductance of 60 or 80 pS respectively. We have determined the A7r5 express Cx40 in the form of a 70 pS channel and Cx43 as 108 and 141 pS channel. And finally we show that human coronary appear to express Cx40 exclusively, yet have two channel sizes with conductances of 52 and 104 pS. We further demonstrate that the effect of oleic acid (OA), the predominant fatty acid found in the cell membrane differs in its effect on the A7r5 vs. heart cells. The A7r5 cells responded with a rapid uncoupling to ∼50% at low dose, and did not further uncouple with increasing concentrations. Single channel analysis suggests the 70 pS channel was very sensitive to OA. The 140 pS channel appeared to be insensitive to OA. Lastly, we examined the effect of the monoamine, serotonin on gap junctions from vessel beds known to differ in their regulation. Junctional conductance and dye-coupling was increased on both long- and short-term exposure to 1,5, or 10 μM doses in all cell types. In the pig coronary cells and the rat mesentery, no change in unitary conductance was observed. The relative frequencies of the channel populations were shifted in both the A7r5 and the human coronary cells. These data support the conclusion that multiple strategies exist for gap junction regulation.