Metabolic communication from cardiac myocytes to vascular endothelial cells.
The endothelium releases substances that affect both vascular and cardiac myocytes. However, under conditions of augmented metabolic demands and cardiac work, signals from the cardiac myocytes may be critical for the endothelium to fulfill its secretory and regulatory function in the vascular bed. Therefore, we hypothesized that cardiac myocytes produce substances that alter the resting membrane potential of endothelial cells and thus vascular tone. Isolated rat cardiac myocytes were electrically stimulated at the rate of 0 and 400 beats/min (Po2 = 150 mmHg), and supernatants were collected from each group (Sup-0; control) and (Sup-400) and used within 6 mo. These supernatants were applied to human coronary endothelial cells that were subsequently analyzed by using the whole cell and cell-attached patch-clamp modes. Sup-0 had no effect on the whole cell current and the zero-current potential. The Sup-0 from myocytes treated with aprotinin, an inhibitor of kallikrein and serine protease, reduced whole cell current between -120 and -60 mV. Sup-400 depolarized endothelial cells from the resting membrane potential of -45 to -5 mV (P < 0.05), increased the magnitude of an inward current, and activated an outward current. Moreover, Sup-400 cells assayed in cell-attached patches increased single channel amplitude and the probability of a channel being in the open state. These effects were reversed by the Sup-400 from aprotinin-treated cells. We conclude that under certain metabolic conditions, isolated cardiac myocytes produce and release vasoactive substances that alter the function of K+ channels in vascular endothelial cells. Thus cardiac myocytes seem to communicate metabolic information to the endothelium, which could potentially influence vascular tone.
Brzezinska
Anna K
AK
Department of Physiology, and the Cardiovascular Center, Medical College of Wisconsin, Milwaukee Wisconsin, USA. abrzez@lsuhsc.edu
Merkus
Daphne
D
Chilian
William M
WM
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D010100:Oxygen