Heterogeneity of L-type calcium current density in coronary smooth muscle

D. K. Bowles, Q. Hu, M. H. Laughlin, Michael Sturek

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Heterogeneity of vascular responses to physiological and pharmacological stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the cellular mechanisms for this heterogeneity are unknown, one plausible may be heterogeneous distribution of ion channels important in regulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that these channels would be unequally distributed throughout the coronary arterial bed. To test this hypothesis, voltage-gated Ca2+ current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 μm), and large arterioles (75- 125 μm) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier, voltage-gated Ca2+ current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM Ba2+) were increased ~2.5- and ~1.5-fold in large arterioles and small arteries, respectively, compared with conduit arteries (-5.58 ± 0.53, -3.54 ± 0.34, and -2.26 ± 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small arteries demonstrated increased inward current at membrane potentials within the physiological range for vascular smooth muscle (as negative -40 mV) compared with conduit arteries. In addition, cells from large arterioles showed a negative shift in the membrane potential for half-maximal activation compared with small and conduit arteries (-13.23 ± 0.88, -6.22 ± 1.35, and -8.62 ± 0.81 mV, respectively; P <0.05). Voltage characteristics and dihydropyridine sensitivity identified this Ca2+ current as predominantly L-type current in all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial vasculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circulation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume273
Issue number4 42-4
StatePublished - 1997
Externally publishedYes

Fingerprint

Smooth Muscle
Arteries
Calcium
Arterioles
Blood Vessels
Coronary Circulation
Membrane Potentials
Miniature Swine
Patch-Clamp Techniques
Ion Channels
Vascular Smooth Muscle
Pharmacology

Keywords

  • Dihydropyridine
  • Vascular smooth muscle
  • Voltage clamp

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Heterogeneity of L-type calcium current density in coronary smooth muscle. / Bowles, D. K.; Hu, Q.; Laughlin, M. H.; Sturek, Michael.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 273, No. 4 42-4, 1997.

Research output: Contribution to journalArticle

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abstract = "Heterogeneity of vascular responses to physiological and pharmacological stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the cellular mechanisms for this heterogeneity are unknown, one plausible may be heterogeneous distribution of ion channels important in regulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that these channels would be unequally distributed throughout the coronary arterial bed. To test this hypothesis, voltage-gated Ca2+ current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 μm), and large arterioles (75- 125 μm) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier, voltage-gated Ca2+ current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM Ba2+) were increased ~2.5- and ~1.5-fold in large arterioles and small arteries, respectively, compared with conduit arteries (-5.58 ± 0.53, -3.54 ± 0.34, and -2.26 ± 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small arteries demonstrated increased inward current at membrane potentials within the physiological range for vascular smooth muscle (as negative -40 mV) compared with conduit arteries. In addition, cells from large arterioles showed a negative shift in the membrane potential for half-maximal activation compared with small and conduit arteries (-13.23 ± 0.88, -6.22 ± 1.35, and -8.62 ± 0.81 mV, respectively; P <0.05). Voltage characteristics and dihydropyridine sensitivity identified this Ca2+ current as predominantly L-type current in all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial vasculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circulation.",
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AU - Hu, Q.

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AU - Sturek, Michael

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N2 - Heterogeneity of vascular responses to physiological and pharmacological stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the cellular mechanisms for this heterogeneity are unknown, one plausible may be heterogeneous distribution of ion channels important in regulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that these channels would be unequally distributed throughout the coronary arterial bed. To test this hypothesis, voltage-gated Ca2+ current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 μm), and large arterioles (75- 125 μm) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier, voltage-gated Ca2+ current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM Ba2+) were increased ~2.5- and ~1.5-fold in large arterioles and small arteries, respectively, compared with conduit arteries (-5.58 ± 0.53, -3.54 ± 0.34, and -2.26 ± 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small arteries demonstrated increased inward current at membrane potentials within the physiological range for vascular smooth muscle (as negative -40 mV) compared with conduit arteries. In addition, cells from large arterioles showed a negative shift in the membrane potential for half-maximal activation compared with small and conduit arteries (-13.23 ± 0.88, -6.22 ± 1.35, and -8.62 ± 0.81 mV, respectively; P <0.05). Voltage characteristics and dihydropyridine sensitivity identified this Ca2+ current as predominantly L-type current in all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial vasculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circulation.

AB - Heterogeneity of vascular responses to physiological and pharmacological stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the cellular mechanisms for this heterogeneity are unknown, one plausible may be heterogeneous distribution of ion channels important in regulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that these channels would be unequally distributed throughout the coronary arterial bed. To test this hypothesis, voltage-gated Ca2+ current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 μm), and large arterioles (75- 125 μm) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier, voltage-gated Ca2+ current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM Ba2+) were increased ~2.5- and ~1.5-fold in large arterioles and small arteries, respectively, compared with conduit arteries (-5.58 ± 0.53, -3.54 ± 0.34, and -2.26 ± 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small arteries demonstrated increased inward current at membrane potentials within the physiological range for vascular smooth muscle (as negative -40 mV) compared with conduit arteries. In addition, cells from large arterioles showed a negative shift in the membrane potential for half-maximal activation compared with small and conduit arteries (-13.23 ± 0.88, -6.22 ± 1.35, and -8.62 ± 0.81 mV, respectively; P <0.05). Voltage characteristics and dihydropyridine sensitivity identified this Ca2+ current as predominantly L-type current in all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial vasculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circulation.

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