Airway smooth muscle excitation-contraction coupling and airway hyperresponsiveness

2005 ◽  
Vol 83 (8-9) ◽  
pp. 725-732 ◽  
Author(s):  
Simon Hirota ◽  
Peter B Helli ◽  
Adriana Catalli ◽  
Allyson Chew ◽  
Luke J Janssen
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Signaling Pathways ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Rho Kinase ◽  
Shortness Of Breath ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Hallmark Feature

The primary complaints from patients with asthma pertain to function of airway smooth muscle (ASM) function including shortness of breath, wheezing, and coughing. Thus, it is imperative to better understand the mechanisms underlying excitation-contraction coupling in ASM. Here, we review the various signaling pathways underlying contraction in ASM, and then examine how these are altered in asthma and airway hyperresponsiveness (a hallmark feature of asthma). Throughout, we highlight how studies of vascular smooth muscle have helped or hindered progress in understanding ASM physiology and pathophysiology.Key words: airway smooth muscle, vascular smooth muscle, excitation-contraction coupling, calcium, Rho-kinase.

Muscarinic excitation-contraction coupling mechanisms in tracheal and bronchial smooth muscles

2001 ◽  
Vol 91 (3) ◽  
pp. 1142-1151 ◽  
Author(s):  
Luke J. Janssen ◽  
Jennifer Wattie ◽  
Hwa Lu-Chao ◽  
Tracy Tazzeo
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Smooth Muscles ◽  
Rho Kinase ◽  
Cyclopiazonic Acid ◽  
Organ Bath ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Coupling Mechanisms ◽  
Sustained Responses

We investigated the mechanisms underlying muscarinic excitation-contraction coupling in canine airway smooth muscle using organ bath, fura 2 fluorimetric, and patch-clamp techniques. Cyclopiazonic acid (CPA) augmented the responses to submaximal muscarinic stimulation in both tracheal (TSM) and bronchial smooth muscles (BSM), consistent with disruption of the barrier function of the sarcoplasmic reticulum. During maximal stimulation, however, CPA evoked substantial relaxation in TSM but not BSM. CPA reversal of carbachol tone persisted in the presence of tetraethylammoium or high KCl, suggesting that hyperpolarization is not involved; CPA relaxations were absent in tissues preconstricted with KCl alone or by permeabilization with β-escin, ruling out a nonspecific effect on the contractile apparatus. Peak contractions were sensitive to inhibitors of tyrosine kinase (genistein) or Rho kinase (Y-27632). Sustained responses were dependent on Ca2+influx in TSM but not BSM; this influx was sensitive to Ni2+ but not La3+. In conclusion, there are several mechanisms underlying excitation-contraction coupling in airway smooth muscle, the relative importance of which varies depending on tissue and degree of stimulation.

Ionic mechanisms and Ca2+ regulation in airway smooth muscle contraction: do the data contradict dogma?

2002 ◽  
Vol 282 (6) ◽  
pp. L1161-L1178 ◽  
Author(s):  
Luke J. Janssen
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Channel Blockers ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Spatial And Temporal Heterogeneity ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Ionic Mechanisms

In general, excitation-contraction coupling in muscle is dependent on membrane depolarization and hyperpolarization to regulate the opening of voltage-dependent Ca2+ channels and, thereby, influence intracellular Ca2+ concentration ([Ca2+]i). Thus Ca2+ channel blockers and K+ channel openers are important tools in the arsenals against hypertension, stroke, and myocardial infarction, etc. Airway smooth muscle (ASM) also exhibits robust Ca2+, K+, and Cl− currents, and there are elaborate signaling pathways that regulate them. It is easy, then, to presume that these also play a central role in contraction/relaxation of ASM. However, several lines of evidence speak to the contrary. Also, too many researchers in the ASM field view the sarcoplasmic reticulum as being centrally located and displacing its contents uniformly throughout the cell, and they have focused almost exclusively on the initial single [Ca2+] spike evoked by excitatory agonists. Several recent studies have revealed complex spatial and temporal heterogeneity in [Ca2+]i, the significance of which is only just beginning to be appreciated. In this review, we will compare what is known about ion channels in ASM with what is believed to be their roles in ASM physiology. Also, we will examine some novel ionic mechanisms in the context of Ca2+ handling and excitation-contraction coupling in ASM.

Sign in / Sign up

Export Citation Format

Share Document