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(Circulation Research. 2000;87:896.)
© 2000 American Heart Association, Inc.

Cellular Biology

Vascular Smooth Muscle Cells Express the _1A Subunit of a P-/Q-Type Voltage-Dependent Ca²⁺Channel, and It Is Functionally Important in Renal Afferent Arterioles

Pernille B. Hansen, Boye L. Jensen, Ditte Andreasen, Ulla G. Friis, Ole Skøtt

From the Department of Physiology and Pharmacology, University of Southern Denmark–Odense University, Odense, Denmark.

Correspondence to Boye L. Jensen, MD, PhD, Department of Physiology and Pharmacology, University of Southern Denmark–Odense University, Winsloewparken 21,3. DK-5000 Odense C, Denmark. E-mail bljensen{at}health.sdu.dk

Abstract—In the present study, we tested whether the _1A subunit, which encodes a neuronal isoform of voltage-dependent Ca²⁺ channels (VDCCs) (P-/Q-type), was present and functional in vascular smooth muscle and renal resistance vessels. By reverse transcription–polymerase chain reaction and Southern blotting analysis, mRNA encoding the _1A subunit was detected in microdissected rat preglomerular vessels and vasa recta, in cultures of rat preglomerular vascular smooth muscle cells (VSMCs), and in cultured rat mesangial cells. With immunoblots, _1A subunit protein was demonstrated in rat aorta, brain, aortic smooth muscle cells (A7r5), VSMCs, and mesangial cells. Immunolabeling with an anti-_1A antibody was positive in acid-macerated, microdissected preglomerular vessels and in A7r5 cells. Patch-clamp experiments on aortic A7r5 cells showed 22±4% (n=6) inhibition of inward Ca²⁺ current by -Agatoxin IVA (10^–8 mol/L), which in this concentration is a specific inhibitor of P-type VDCCs. Measurements of intracellular Ca²⁺ in afferent arterioles with fluorescence-imaging microscopy showed 32±9% (n=10) inhibition of the K⁺-induced rise in Ca²⁺ in the presence of 10^–8 mol/L -Agatoxin IVA. In microperfused rabbit afferent arterioles, -Agatoxin IVA inhibited depolarization-mediated contraction with an EC₅₀ of 10^–17 mol/L and complete blockade at 10^–14 mol/L. We conclude that the _1A subunit is expressed in VSMCs from renal preglomerular resistance vessels and aorta, as well as mesangial cells, and that P-type VDCCs contribute to Ca²⁺ influx in aortic and renal VSMCs and are involved in depolarization-mediated contraction in renal afferent arterioles.

Key Words: smooth muscle • voltage-dependent Ca²⁺ channel • renal • arteriole

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