Calmodulin mediates norepinephrine-induced receptor-operated calcium entry in preglomerular resistance arteries.
Although L-type voltage-dependent calcium channels play a major role in mediating vascular smooth muscle cell contraction in the renal vasculature, non-L-type calcium entry mechanisms represent a significant component of vasoactive agonist-induced calcium entry in these cells as well. To investigate the role of these non-voltage-dependent calcium entry pathways in the regulation of renal microvascular reactivity, we have characterized the function of store- and receptor-operated channels (SOCs and ROCs) in renal cortical interlobular arteries (ILAs) of rats. Using fura 2-loaded, microdissected ILAs, we find that the L-type channel antagonist nifedipine blocks less than half the rise in intracellular calcium concentration ([Ca(2+)](i)) elicited by norepinephrine. SOCs were activated in these vessels using the sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitors cyclopiazonic acid and thapsigargin and were dose dependently blocked by the SOC antagonists Gd(3+) and 2-aminoethoxydiphenyl borate (2-APB) and the combined SOC/ROC antagonist SKF-96365. Gd(3+) had no effect on the non-L-type Ca(2+) entry activated by 1 microM NE. A low concentration of SKF-96365 that did not affect thapsigargin-induced store-operated Ca(2+) entry blocked 60-70% of the NE-induced Ca(2+) entry. Two different calmodulin inhibitors (W-7 and trifluoperazine) also blocked the NE-induced Ca(2+) entry. These data suggest that in addition to L-type channels, NE primarily activates ROCs rather than SOCs in ILAs and that this receptor-operated Ca(2+) entry mechanism is regulated by calmodulin. Interestingly, 2-APB completely blocked the NE-induced non-L-type Ca(2+) entry, implying that SOCs and ROCs in preglomerular resistance vessels share a common molecular structure.
Facemire
Carie S
CS
Dept. of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, NC 27599-7545, USA.
Arendshorst
William J
WJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000502:physiology*; D012077:Renal Artery / Q000502:physiology*; D015398:Signal Transduction
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002147:Calmodulin; D044169:Receptors, Calcium-Sensing; D009638:Norepinephrine