Intracranial-extracranial differences in the Ca2+ sensitivity of rabbit arteries

We have previously demonstrated that the ratio of calcium uptake to force production varies widely with age, artery size, and method of contraction in cerebral arteries. The present experiments were conducted to examine the possibility that these differences involve corresponding variations in contractile force-calcium relations. Common carotid (COM), basilar (BAS), and middle cerebral (MCA) arteries from adult were denuded of endothelium and mounted in vitro for measurement of contractility. Following equilibration at optimum resting diameter, the arteries were permeabilized (beta-escin, 50 microg/ml) and depleted of intracellular Ca2+ by treatment with 1 microM A23187. Ca2+ depletion was verified by absence of any contracile response to either 25 mM caffeine or 1 microM inositol 1,4,5-trisphosphate. Then, in the continuous presence of 1 microM calmodulin, bath calcium concentration was raised from zero through 10 microM in half-log increments and the corresponding contractions were recorded. For all permeabilized arteries, the maximum force produced by 10 microM Ca was greater than or equal to that produced by 120 mM potassium-Krebs in the same segment before skinning. The pD2 (-log ED50) values for calcium averaged 6.39 +/- 0.03, 6.77 +/- 0.04, and 6.92 +/- 0.03 in COM, BA, and MCA segments, respectively. In arteries contracted by a constant submaximal concentration of calcium (0.1 microM for BAS and MCA, 0.3 microM for COM), the addition of 5HT produced a dose-dependent and GDPbetaS-sensitive increase in tension of up to 44% maximum. GTPgammaS mimicked the effects of 5HT and prevented further increases in Ca force induced by 5HT. Together, these data demonstrate that cerebrovascular calcium sensitivity is an anatomically heterogenous, physiologically regulated parameter responsive to agonist-induced perturbations.