This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nazarov, V. Articles by Dietrich, H. H. Search for Related Content PubMed PubMed Citation Articles by Nazarov, V. Articles by Dietrich, H. H. Related Collections Other Vascular biology Calcium cycling/excitation-contraction coupling Cell signalling/signal transduction Brain Circulation and Metabolism Ion channels/membrane transport

(Stroke. 2000;31:2500.)
© 2000 American Heart Association, Inc.

Original Contributions

Extracellular pH, Ca²⁺ Influx, and Response of Vascular Smooth Muscle Cells to 5-Hydroxytryptamine

Vitaly Nazarov, MD, PhD; Janette Aquino-DeJesus, MD Michael Apkon, MD, PhD

From the Departments of Pediatrics (V.N., J.A-D., M.A.) and Cellular and Molecular Physiology (M.A.), Yale University School of Medicine, New Haven, Conn.

Correspondence to Michael Apkon, MD, PhD, Department of Pediatrics, Yale University, PO Box 208064, New Haven, CT 06520-8064. E-mail michael.apkon{at}yale.edu

Background and Purpose—Cerebral vascular smooth muscle cells (VSMCs) contract on extracellular pH (pH_o) increases and relax on pH_o decreases. These changes in tone are believed to result from changes in [Ca²⁺]_i, although the responsible mechanisms are not fully understood. VSMCs also contract in response to 5-hydroxytryptamine (5-HT), which increases [Ca²⁺]_i via both Ca²⁺ release and influx. We hypothesized that examining effects of pH_o decreases on 5-HT–induced [Ca²⁺]_i changes would allow us to identify mechanisms whereby pH_o influences tone. Accordingly, we compared [Ca²⁺]_i increases in cerebral VSMCs, evoked by 5-HT, with increases evoked by increased pH_o and examined 5-HT–dependent [Ca²⁺]_i increases at normal and decreased pH_o.

Methods—We monitored [Ca²⁺]_i,, using the Ca²⁺-sensitive dye fura 2, in cultured rat cerebral VSMCs obtained by enzymatic digestion of middle cerebral arteries and their branches (passages 1 to 3) grown on glass coverslips and superfused with physiological saline.

Results—Increasing pH_o from 7.3 to 7.8 increased [Ca²⁺]_i, and these increases were prevented in Ca²⁺-free solutions. Decreasing pH_o from 7.3 to 6.9 did not alter [Ca²⁺]_i unless [Ca²⁺]_i was first raised by treatment with 5-HT (10 µmol/L). 5-HT resulted in biphasic [Ca²⁺]_i increases characterized by transient peaks blocked by the Ca²⁺-ATPase inhibitor thapsigargin (10 nmol/L) and prolonged plateaus blocked by the Ca²⁺ channel blocker Ni²⁺ (1 mmol/L). Acidification did not alter the transient peaks but significantly reduced 5-HT–induced Ca²⁺ influx.

Conclusions—We conclude that increasing pH_o induces Ca²⁺ influx in rat cerebral VSMCs and decreasing pH_o inhibits 5-HT–stimulated Ca²⁺ entry but not intracellular Ca²⁺ release.

Editorial Comment

Hans H. Dietrich, PhD, Guest Editor

Department of Neurosurgery Washington University School of Medicine St Louis, Missouri

This article has been cited by other articles:

				Y. K. B. Siddegowda, M. D. M. Leo, D. Kumar, O. K. Hooda, V. R. Prakash, and S. K. Mishra Vascular: Influence of heat stress on the reactivity of isolated chicken carotid artery to vasoactive agents Exp Physiol, November 1, 2007; 92(6): 1077 - 1086. [Abstract] [Full Text] [PDF]