GAP JUNCTION FUNCTION IN VASCULAR SMOOTH-MUSCLE - INFLUENCE OF SEROTONIN

In this study we examined the effects of serotonin (5-hydroxytryptamine, 5-HT) on the function of gap junctions between smooth muscle cells isolated from human and pig coronary and rat mesentery arteries and between A7r5 cells (cell line derived from embryonic rat aorta). Mesentery and pig coronary cells expressed connexin (Cx) 43, and human coronary cells expressed Cx40. Mesentery and pig coronary cells each exhibited a single gap junction channel population with unitary conductances of 75 and 59 pS, respectively. Human coronary cells exhibited two channel populations with unitary conductances of 51 and 107 pS. The A7r5 cells express Cx40 and Cx43 and exhibit three channel populations with unitary conductances of 70, 108, and 141 pS. Under control conditions, junctional conductance between the four cell types ranged from 11 to 20 nS. During maximal stimulation with 5-HT (1-10 mu M), junctional conductance increased (29-75%) in all four cell types. The unitary conductance profiles in the rat mesentery and pig coronary cells were unaffected by 5-HT, suggesting that the observed increase in macroscopic conductance reflects an increase in open probability. Unitary conductances were also unaffected in the human coronary and A7r5 cells. However, there was a reduced frequency of the 105-pS channel in the human coronary cells and of the 70- and 141-pS channels in the A7r5 cells. These changes in the relative frequency histograms suggest that the open probabilities of the various channel types are differentially affected by the 5-HT treatment. Thus the data suggest that vascular smooth muscle cells exhibit a variety of channel types whose open probabilities are differentially affected by 5-HT stimulation.