TRPV4 Activation During Guinea Pig Airway Smooth Muscle Contraction Promotes Ca and Na Influx

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2024 Mar 28

PMID 38543079

Authors

Luis M Montano

Abril Carbajal-Garcia

Maria F Casas-Hernandez

David Arredondo-Zamarripa

Jorge Reyes-Garcia

Affiliations

Soon will be listed here.

Abstract

Airway smooth muscle (ASM) contraction is determined by the increase in intracellular Ca concentration ([Ca]) caused by its release from the sarcoplasmic reticulum (SR) or by extracellular Ca influx. Major channels involved in Ca influx in ASM cells are L-type voltage-dependent Ca channels (L-VDCCs) and nonselective cation channels (NSCCs). Transient receptor potential vanilloid 4 (TRPV4) is an NSCC recently studied in ASM. Mechanical stimuli, such as contraction, can activate TRPV4. We investigated the possible activation of TRPV4 by histamine (His)- or carbachol (CCh)-induced contraction in guinea pig ASM. In single myocytes, the TRPV4 agonist (GSK101) evoked an increase in [Ca], characterized by a slow onset and a plateau phase. The TRPV4 antagonist (GSK219) decreased channel activity by 94%, whereas the Ca-free medium abolished the Ca response induced by GSK101. Moreover, GSK101 caused Na influx in tracheal myocytes. GSK219 reduced the Ca peak and the Ca plateau triggered by His or CCh. TRPV4 blockade shifted the concentration-response curve relating to His and CCh to the right in tracheal rings and reduced the maximal contraction. Finally, the activation of TRPV4 in single myocytes increased the Ca refilling of the SR. We conclude that contraction of ASM cells after stimulation with His or CCh promotes TRPV4 activation, the subsequent influx of Ca and Na, and the opening of L-VDCCs. The entry of Ca into ASM cells via TRPV4 and L-VDCCs contributes to optimal smooth muscle contraction.

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