Kk. Hirschi et al., OLEIC-ACID DIFFERENTIALLY AFFECTS GAP JUNCTION-MEDIATED COMMUNICATIONIN HEART AND VASCULAR SMOOTH-MUSCLE CELLS, The American journal of physiology, 265(6), 1993, pp. 30001517-30001526
The effects of oleic acid (OA) on gap junction mediated intercellular
communication between A7r5 cells and neonatal rat cardiac myocytes wer
e determined. In A7r5 cells the extent of dye coupling was influenced
in a biphasic manner by increasing concentrations of OA. Low concentra
tions of OA (0.1-1 muM) reduced the incidence of dye coupling from 90%
(in control cells) to approximately 50%. Further increases in OA conc
entration, up to 100 muM, had no further effect on extent of dye coupl
ing. In contrast, dye coupling between cardiac myocytes was reduced to
near zero levels in a linear fashion by 1-25 muM OA. Whereas high OA
concentrations reduce junctional conductance (g1) between heart cells
to zero [J. M. Burt, K. D. Massey, and B. N. Minnich. Am. J. Physiol.
260 (Cell Physiol. 29): C439-C448, 19911, g(j) between A7r5 cells was
decreased by a maximum of 45% by OA. These differences in OA sensitivi
ty between the two cell types were not explained by differences in the
rate or magnitude of OA uptake by the cells or by differences in the
fraction of incorporated OA accessible to albumin washout, i.e., the p
lasma membrane fraction. Instead, the activity of the individual chann
el types exhibited different sensitivities to OA. In the presence of i
ncreasing concentrations of OA, the activities of first the 70-pS chan
nel population [composed of connexin40 (Cx40)] and then the 108-pS cha
nnel population (composed of Cx43) were diminished, leaving predominan
tly the 140-pS channels (composed of Cx43) at high OA concentrations.
The uncoupling effects of OA in both cell types could be reversed by w
ashout with albumin-containing solution; however, higher concentration
s of albumin and more vigorous wash conditions were required for full
recovery in the A7r5 cells. In addition, albumin also reversed the eff
ects of OA on channel activity. These data suggest that OA binds with
greater affinity to the 70- vs. 108- or 140-pS channels and associated
with binding is reduced channel activity.