INTRACRANIAL-EXTRACRANIAL DIFFERENCES IN THE CA2+ SENSITIVITY OF RABBIT ARTERIES

We have previously demonstrated that the ratio of calcium uptake to fo rce production varies widely with age, artery size, and method of cont raction in cerebral arteries. The present experiments were conducted t o examine the possibility that these differences involve corresponding variations in contractile force-calcium relations. Common carotid (CO M), basilar (BAS), and middle cerebral (MCA) arteries from adult were denuded of endothelium and mounted in vitro for measurement of contrac tility. Following equilibration at optimum resting diameter, the arter ies were permeabilized (beta-escin, 50 mu g/ml) and depleted of intrac ellular Ca2+ by treatment with 1 mu M A23187. Ca2+ depletion was verif ied by absence of any contracile response to either 25 mM caffeine or 1 mu M inositol 1,4,5-trisphosphate. Then, in the continuous presence of 1 mu M calmodulin, bath calcium concentration was raised from zero through 10 mu M in half-log increments and the corresponding contracti ons were recorded. For all permeabilized arteries, the maximum force p roduced by 10 mu M Ca was greater than or equal to that produced by 12 0 mM potassium-Krebs in the same segment before skinning. The pD2 (-lo g ED(50)) values for calcium averaged 6.39 +/- 0.03, 6.77 +/- 0.04, an d 6.92 +/- 0.03 in COM, BA, and MCA segments, respectively. In arterie s contracted by a constant submaximal concentration of calcium (0.1 mu M for BAS and MCA, 0.3 mu M for COM), the addition of 5HT produced a dose-dependent and GDP beta S-sensitive increase in tension of up to 4 4% maximum. GTP gamma S mimicked the effects of 5HT and prevented furt her increases in Ca force induced by 5HT. Together, these data demonst rate that cerebrovascular calcium sensitivity is an anatomically heter ogenous, physiologically regulated parameter responsive to agonist-ind uced perturbations.