. Altered functional coupling of coronary K ϩ channels in diabetic dyslipidemic pigs is prevented by exercise.

No abstract

1 The effects of ryanodine and caffeine on intracellular free Ca2+ concentration ([Ca2+] 5 Cells pretreated with caffeine in 0 Ca PSS, which depleted the caffeine-sensitive sarcoplasmic reticulum Ca2" store, showed no increase in [Ca24], when challenged with 10 fLM ryanodine. The ryanodine-associated increase in [Ca2+],, which was sustained in 0 Ca PSS during the 10 min ryanodine exposure in cells not pretreated with caffeine, suggests that ryanodine releases Ca2+ from the sarcoplasmic reticulum, but also inhibits Ca24 efflux.6 Intracellular free Ba2+ ([Ba24],) was measured with fura-2 microfluorometry to define further the Ca2" efflux pathway inhibited by ryanodine; specifically, Ba2+ is not transported by the Ca2" pump, but will substitute for Ca2" in Na+-Ca24 exchange. In porcine cells pretreated with caffeine in 0 Ca PSS to deplete the caffeine-sensitive sarcoplasmic reticulum Ca2+ store, depolarization with 80 mM K4 in 2 mM external Ba24 caused a 100 ± 6% increase in fura-2 fluorescence ([Ba2+]

SUMMARY1. We tested the hypothesis that the sarcoplasmic reticulum (SR) buffers (attenuates) the increase in averaged myoplasmic free [Ca2+] (Caim)

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.