Voltage-gated divalent currents in descending vasa recta pericytes

Multiple voltage-gated Ca²⁺ 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 Ca²⁺ and Ba²⁺ 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 Ni²⁺ (100 and 1,000 μM), exhibited slow inactivation, and conducted Ba²⁺ > Ca ²⁺ at a ratio of 2.3:1, consistent with "long-lasting" L-type Ca_V. In FPL, with 1 mM Ca²⁺ 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 Ba²⁺ > Ca²⁺ at a ratio of ∼2:1. In Ca²⁺, 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 Ba²⁺, 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 Ba²⁺ 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.