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Heterogeneity of L-type calcium current density in coronary smooth muscle
D K Bowles1, Q Hu, M H Laughlin
1Dalton Cardiovascular Research Center, and Department of Physiology, University of Missouri, Columbia 65211, USA.
Insights
Vascular responses vary by coronary artery size due to differences in voltage-gated calcium channels. L-type calcium channel density is lower in larger arteries, impacting vascular tone regulation.
Area of Science:
- Cardiovascular Physiology
- Ion Channel Biology
- Vascular Smooth Muscle Research
Background:
- Vascular responses in the coronary circulation exhibit heterogeneity, often linked to vessel size.
- The cellular mechanisms underlying this heterogeneity, particularly ion channel distribution, remain largely unknown.
- Voltage-gated calcium channels are critical for regulating vascular tone.
Purpose of the Study:
- To investigate the hypothesis that voltage-gated calcium channels are heterogeneously distributed across the coronary arterial bed.
- To determine if calcium channel distribution correlates with arterial diameter.
- To explore the implications for functional heterogeneity in coronary circulation.
Main Methods:
- Whole-cell voltage-clamp techniques were used to measure voltage-gated calcium currents in swine coronary artery smooth muscle.
- Experiments utilized conduit arteries (>1.0 mm), small arteries (200-250 µm), and large arterioles (75-125 µm).
- Calcium (2 mM) or Barium (10 mM) served as the charge carrier.
Main Results:
- Calcium current density was inversely related to arterial diameter: large arterioles > small arteries > conduit arteries.
- Peak inward currents (10 mM Ba2+) were significantly higher in large arterioles and small arteries compared to conduit arteries.
- Cells from large arterioles exhibited a negative shift in the membrane potential for half-maximal activation compared to smaller and conduit arteries.
Conclusions:
- L-type calcium channel current density is inversely proportional to arterial diameter in the coronary vasculature.
- This heterogeneous distribution of calcium channels likely contributes to the functional heterogeneity observed in the coronary circulation.
- Understanding this heterogeneity is crucial for comprehending coronary vascular regulation.
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 factor 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 microm), and large arterioles (75-125 microm) 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 approximately 2.5- and approximately 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 as -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.