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

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 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 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.

Gender-specific K+-channel contribution to adenosine-induced relaxation in coronary arterioles

“…We also found no sex difference in endothelin concentration required to attain similar levels of preconstriction. This finding is in contrast to those of others using larger porcine coronary arteries (14,24) and supports heterogeneity in physiological and pharmacological responses in vessels of different sizes (4,15,20).…”

“…Whole cell currents were determined by using a standard whole cell voltage-clamp technique as used routinely (4). Cells were initially superfused with low-Ca 2ϩ PSS containing (in mM) 138 NaCl, 5 KCl, 0.1 CaCl2, 1 MgCl2, 10 glucose, and 20 HEPES, pH 7.4, during gigaseal formation.…”

Effects of Unoprostone and Endothelin 1 on L-Type Channel Currents in Human Trabecular Meshwork Cells

“…The inhibiting effect of unoprostone seems to be mediated by tyrosine kinases. L-type current density in the TM is higher than that observed in other smooth muscle tissues [19][20][21] . In addition to smooth muscle function, the TM is a secretory tissue involved in the secretion of numerous components of the extracellular matrix like matrix metalloproteinases and tissue inhibitors of metalloproteinase [22][23][24] .…”

Exaggerated coronary vasoreactivity to endothelin-1 in aged rats: Role of protein kinase C

“…Isolated CSM cells were obtained by enzymatic dispersion for voltage-clamp experiments as described previously [24][25][26]. Cell suspensions were stored in low Ca 2+ (0.1 mM) buffer at 4 8C until use (0-6 h).…”