Voltage-gated divalent currents in descending vasa recta pericytes.
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.
Zhang
Zhong
Z
Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Lin
Hai
H
Cao
Chunhua
C
Khurana
Sandeep
S
Pallone
Thomas L
TL
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D007679:Kidney Medulla / Q000166:cytology / Q000378:metabolism*; D020748:Mibefradil / Q000494:pharmacology; D023421:Models, Animal; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D020867:omega-Agatoxin IVA / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011758:Pyrroles; D020867:omega-Agatoxin IVA; C071658:FPL 64176; D001464:Barium; D020748:Mibefradil; D009532:Nickel; D009543:Nifedipine; D002118:Calcium