Voltage-gated divalent currents in descending vasa recta pericytes

Zhong Zhang, Hai Lin, Chunhua Cao, Sandeep Khurana, Thomas L. Pallone

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15 Scopus citations

Abstract

Multiple voltage-gated Ca2+ channel (CaV) 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 CaV currents of pericytes that contract descending vasa recta (DVR). The dihydropyridine CaV 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 CaV. In FPL, with 1 mM Ca2+ as charge carrier, Boltzmann fits yielded half-maximal activation potential (V1/2) 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 CaV 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 V1/2 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.

Original languageEnglish (US)
Pages (from-to)F862-F871
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number4
DOIs
Publication statusPublished - Oct 1 2010

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Keywords

  • Barium
  • Calcium
  • Ion channel
  • Mibefradil
  • Patch clamp

ASJC Scopus subject areas

  • Physiology
  • Urology

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