Voltage-gated divalent currents in descending vasa recta pericytes

Abstract

Multiple voltage-gated Ca(2+) channel (Ca(V)) subtypes have been reported to participate in control of the juxtamedullary glomerular arterioles of the kidney. Using the patch-clamp technique, we examined whole cell Ca(V) currents of pericytes that contract descending vasa recta (DVR). The dihydropyridine Ca(V) agonist FPL64176 (FPL) stimulated inward Ca(2+) and Ba(2+) currents that activated with threshold depolarizations to -40 mV and maximized between -20 and -10 mV. These currents were blocked by nifedipine (1 μM) and Ni(2+) (100 and 1,000 μM), exhibited slow inactivation, and conducted Ba(2+) > Ca(2+) at a ratio of 2.3:1, consistent with "long-lasting" L-type Ca(V). In FPL, with 1 mM Ca(2+) as charge carrier, Boltzmann fits yielded half-maximal activation potential (V(1/2)) and slope factors of -57.9 mV and 11.0 for inactivation and -33.3 mV and 4.4 for activation. In the absence of FPL stimulation, higher concentrations of divalent charge carriers were needed to measure basal currents. In 10 mM Ba(2+), pericyte Ca(V) currents activated with threshold depolarizations to -30 mV, were blocked by nifedipine, exhibited voltage-dependent block by diltiazem (10 μM), and conducted Ba(2+) > Ca(2+) at a ratio of ∼2:1. In Ca(2+), Boltzmann fits to the data yielded V(1/2) and slope factors of -39.6 mV and 10.0 for inactivation and 2.8 mV and 7.7 for activation. In Ba(2+), V(1/2) and slope factors were -29.2 mV and 9.2 for inactivation and -5.6 mV and 6.1 for activation. Neither calciseptine (10 nM), mibefradil (1 μM), nor ω-agatoxin IVA (20 and 100 nM) blocked basal Ba(2+) currents. Calciseptine (10 nM) and mibefradil (1 μM) also failed to reverse ANG II-induced DVR vasoconstriction, although raising mibefradil concentration to 10 μM was partially effective. We conclude that DVR pericytes predominantly express voltage-gated divalent currents that are carried by L-type channels.

Syncytial communication in descending vasa recta includes myoendothelial coupling

“…This is consistent with a putative role for the endothelial layer to exert a tonic relaxant effect by lowering voltage-gated calcium entry into pericytes. Prior investigations showed that L-type VGCC dominate as a route for agonistinduced calcium entry into pericytes and juxtamedullary effer- ent arterioles (25,56). The close identity of membrane potentials in E-E, P-P, E-P, and P-E studies implies, for a given vessel, that all membrane potentials lie within a narrow range.…”

“…Pericytes express voltagegated calcium channels (VGCC) the open probability of which is enhanced by depolarization (43,56,59). Inhibition L-type VGCC blocks pericyte calcium entry, DVR contraction, and may enhance renal medullary blood flow (24,31,50,56,58,59). In turn, the membrane potential that governs pericyte VGCC is regulated by the balanced activity of calcium-activated chloride channels, several classes of K ϩ channels, and a hyperpolarizing influence of ouabain-sensitive electrogenic Na ϩ , K ϩ exchange (4,30,33,35).…”

Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

“…They regulate vascular tone, blood flow (41,76), and capillary diameter (78). In the kidney, medullary pericytes have been studied in greatest detail (74,76,111,112). Medullary pericytes line the descending vasa recta in greatest density, and relatively spare the ascending vasa recta.…”

Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

“…In a recent study of calcium current in rat vasa recta pericytes, P/Q-type antagonist had no effect on calcium currents, 21 in contrast to rat preglomerular myocytes. 4 However, endothelial cells were not investigated.…”