Carbon monoxide dilates cerebral arterioles by enhancing the coupling of Ca2+ sparks to Ca2+-activated K+ channels

Jonathan Jaggar, Charles Leffler, Serguei Y. Cheranov, Dilyara Tcheranova, Shuyu E, Xiaoyang Cheng

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Carbon monoxide (CO) is generated endogenously by the enzyme heme oxygenase. Although CO is a known vasodilator, cellular signaling mechanisms are poorly understood and are a source of controversy. The goal of the present study was to investigate mechanisms of CO dilation in porcine cerebral arterioles. Data indicate that exogenous or endogenously produced CO is a potent activator of large-conductance Ca2+-activated K+ (KCa) channels and Ca2+ spark-induced transient KCa currents in arteriole smooth muscle cells. In contrast, CO is a relatively poor activator of Ca2+ sparks. To understand the apparent discrepancy between potent effects on transient KCa currents and weak effects on Ca2+ sparks, regulation of the coupling relationship between these events by CO was investigated. CO increased the percentage of Ca2+ sparks that activated a transient KCa current (ie, the coupling ratio) from ≈62% in the control condition to 100% and elevated the slope of the amplitude correlation between these events ≈2.6-fold, indicating that Ca2+ sparks induced larger amplitude transient KCa currents in the presence of CO. This signaling pathway for CO is physiologically relevant because ryanodine, a ryanodine-sensitive Ca2+ release channel blocker that inhibits Ca2+ sparks, abolished CO dilation of pial arterioles in vivo. Thus, CO dilates cerebral arterioles by priming KCa channels for activation by Ca2+ sparks. This study presents a novel dilatory signaling pathway for CO in the cerebral circulation and appears to be the first presents of a vasodilator that acts by increasing the effective coupling of Ca2+ sparks to KCa channels.

Original languageEnglish (US)
Pages (from-to)610-617
Number of pages8
JournalCirculation research
Volume91
Issue number7
DOIs
StatePublished - Oct 4 2002

Fingerprint

Calcium-Activated Potassium Channels
Arterioles
Carbon Monoxide
Ryanodine
Vasodilator Agents
Dilatation
Cerebrovascular Circulation
Heme Oxygenase (Decyclizing)
Smooth Muscle Myocytes
Swine

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Carbon monoxide dilates cerebral arterioles by enhancing the coupling of Ca2+ sparks to Ca2+-activated K+ channels. / Jaggar, Jonathan; Leffler, Charles; Cheranov, Serguei Y.; Tcheranova, Dilyara; E, Shuyu; Cheng, Xiaoyang.

In: Circulation research, Vol. 91, No. 7, 04.10.2002, p. 610-617.

Research output: Contribution to journalArticle

Jaggar, Jonathan ; Leffler, Charles ; Cheranov, Serguei Y. ; Tcheranova, Dilyara ; E, Shuyu ; Cheng, Xiaoyang. / Carbon monoxide dilates cerebral arterioles by enhancing the coupling of Ca2+ sparks to Ca2+-activated K+ channels. In: Circulation research. 2002 ; Vol. 91, No. 7. pp. 610-617.
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