title: Voltage-gated Ca2+ entry and ryanodine receptor Ca2+-induced Ca2+ release in preglomerular arterioles.
abstract: We have previously shown that in afferent arterioles, angiotensin II (ANG II) involves activation of the inositol trisphosphate receptor (IP(3)R), activation of adenine diphosphoribose (ADPR) cyclase, and amplification of the initial IP(3)R-stimulated release of cytosolic Ca(2+) ([Ca(2+)](i)) from the sarcoplasmic reticulum (SR) (Fellner SK, Arendshorst WJ. Am J Physiol Renal Physiol 288: F785-F791, 2004). The response of the ryanodine receptor (RyR) to local increases in [Ca(2+)](i) is defined as calcium-induced calcium release (CICR). To investigate whether Ca(2+) entry via voltage-gated channels (VGCC) can stimulate CICR, we treated fura 2-loaded, freshly isolated afferent arterioles with KCl (40 mM; high KCl). In control arterioles, peak [Ca(2+)](i) increased by 165 +/- 10 nM. Locking the RyR in the closed position with ryanodine (100 microM) inhibited the [Ca(2+)](i) response by 59% (P < 0.01). 8-Br cADPR, a specific blocker of the ability of cyclic ADPR (cADPR) to sensitize the RyR to Ca(2+), caused a 43% inhibition. We suggest that the lower inhibition by 8-Br cADPR (P = 0.02, ryanodine vs. 8-Br cADPR) represents endogenously active ADPR cyclase. Depletion of SR Ca(2+) stores by inhibiting the SR Ca(2+)-ATPase with cyclopiazonic acid or thapsigargin blocked the [Ca(2+)](i) responses to KCl by 51% (P not significant vs. ryanodine or 8-Br cADPR). These data suggest that about half of the increase in [Ca(2+)](i) induced by high KCl is accomplished by activation of CICR through the ability of entered Ca(2+) to expose the RyR to high local concentrations of Ca(2+) and that endogenous cADPR contributes to the process.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA. sfellner@med.unc.edu
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fellner
authors.forename: William J
authors.initials: WJ
authors.lastname: Arendshorst
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply*; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D011189:Potassium Chloride; D002118:Calcium