Abstract
1.. We have studied the effects of the metabolic inhibitors cyanide (CN) and deoxyglucose (DG) on the intracellular Ca2+ concentration ([Ca2+](i)) in macrovascular endothelial cells derived from human umbilical vein (EA cells). 2. CN- and DG increased [Ca2+](i) in non-voltage clamped cells. This effect was dependent on extracellular Ca2+ concentration and membrane potential, indicating that CN- induced a Ca2+ entry. 3. During expose to CN- and/or DG, EA cells depolarise. This depolarisation is sometimes preceded by a small, but transient hyperpolarisation due to activation of a big - conductance K+ channels, BK(Ca) present in EA cells. However, in approximately 90% of the cells tested, the CN- and/or DG induced elevation of [Ca2+](i) was insufficient to activate BK(Ca). 4. CN- and/or DG enhanced BK(Ca) currents preactivated by an elevation of [Ca2+](i) via cell dialysis with 0.5 and 1 μM, respectively. Thus, metabolic inhibition sensitises BK(Ca). 5. The CN- induced depolarisation of EA cells occurs by activating a current that reversed at positive membrane potentials. Substituting extracellular cations abolished the inward component of this current by NMDG, indicating that CN- activated a non-selective cation channel, NSC. This current was reduced by extracellular Ca2+ and Mg2+ but is partially carried by Ca2+. 6. It is concluded that CN elevates [Ca2+](i) by activating Ca2+ permeable NSC channels. The properties of these channels are similar to those of the recently described trp3 channels expressed in endothelium.
Original language | English |
---|---|
Pages (from-to) | 155-168 |
Number of pages | 14 |
Journal | Endothelium: Journal of Endothelial Cell Research |
Volume | 7 |
Issue number | 3 |
DOIs | |
State | Published - 2000 |
Bibliographical note
Funding Information:acknowledge support given by the Federal Belgian State (Interuniversity Poles of Attraction Programme, Prime Ministers Office IUAP Nr. 3P4/23), the Flemish Government (F.W.O. (3.0237.95, C.O.F./96/22-A0659), and by the European Commission (BMH4-CT96-0602).
Funding Information:
This project was supported “Levenslijn” (7.002 1.99). SH Suh is supported by Korea Science and Engineering Foundation (1998) and by “Levenslijn”. We also
Keywords
- Ca entry
- Cation channels
- Hypoxia
- Intracellular calcium
- Metabolic inhibition
- Patch clamp