Multiple Ionic Mechanisms Activated by Bradykinin in Coronary Venular Endothelial Cells

In coronary endothelium, bradykinin (BK) modulates production of vasodilators by stimulating Ca2+ influx. To examine the ionic currents involved in this process, we applied BK (100 nM) to single bovine coronary venular endothelial cells (CVEC) while recording membrane potential (Em) or whole-cell current simultaneously with [Ca2+]i. The resting potential (Er) of unstimulated cells was bimodally distributed (-70 ± 9 mV, n = 26; -15 ± 8 mV, n = 30). Irrespective of Er, BK evoked a biphasic [Ca2+]i increase simultaneously with a change in Em. When Er was negative to -30 mV, depolarizations were typically observed. When Er was positive to -30 mV, transient hyperpolarizations were typically observed. Under voltage clamp, [Ca2+], increased as the membrane hyperpolarized and the ratio Δ[Ca2+]i/ΔEm was greater in the presence of BK than in unstimulated cells. Many, but not all, cells exhibited an outward K+ current that appeared to be Ca2+ dependent. When present, this current typically predominated over other currents and resulted in hyperpolarizations. When K+ currents were small or blocked, two inward currents were recorded. The first was a large (-224 ± 20 pA at -70 mV), rapidly activating current carried by Cl-. The second was a smaller (-81 ± 9 pA at -70 mV) cationic current carried in part by Ca2+. These data suggest that BK activates at least three distinct currents in CVECs: a K+-current, a Cl−-current, and a nonselective cation current. The predominance of one or more of these currents in an individual cell presumably determines that cell's electrophysiological response to BK.