HETEROGENEITY OF L-TYPE CALCIUM CURRENT-DENSITY IN CORONARY SMOOTH-MUSCLE

Heterogeneity of vascular responses to physiological and pharmacologic al stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the ce llular mechanisms for this heterogeneity are unknown, one plausible fa ctor may be heterogeneous distribution of ion channels important in re gulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that the se channels would be unequally distributed throughout the coronary art erial bed. To test this hypothesis, voltage-gated Ca2+ current was mea sured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 mu m), and large arterioles (75-125 mu m) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba 2+ 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 similar t o 2.5- and similar to 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 memb rane potentials within the physiological range for vascular smooth mus cle (as negative as -40 mV) compared with conduit arteries. In additio n, 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, res pectively; P < 0.05). Voltage characteristics and dihydropyridine sens itivity identified this Ca2+ current as predominantly L-type current i n all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial va sculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circu lation.