Biomedical Engineering Reference
In-Depth Information
receptors from Ca
2
+
store in myocytes.
22
All 3 types of ryanodine receptors (RyR1-
RyR3) are expressed in smooth myocytes.
In airway smooth myocytes, membrane depolarization does not prime
instantaneous Ca
2
+
release. However, voltage depolarization during sufficiently
long duration (
1 s) can induce local Ca
2
+
release through ryanodine receptors,
independently of Ca
V
channels and associated extracellular Ca
2
+
import into the
cytosol [
720
].
Resulting Ca
2
+
sparks prime cell contraction. The long latency for
depolarization-induced Ca
2
+
release in airway smooth myocytes is explained by
involvement of GPCR that can serve as voltage sensors and their initiated signaling.
This type of mechanism is illustrated by activated M
3
muscarinic receptors in the
absence of exogenous agonists that trigger the Gq-PLC-IP
3
axis. This signaling
pathway provokes a Ca
2
+
release through IP
3
Rs from the sarcoplasmic reticulum
that is then enhanced by that through RyR2 (local Ca
2
+
-induced Ca
2
+
release), but
neither RyR1 nor RyR3 [
720
].
>
8.4.4
Airway Smooth Myocyte Products
Airway smooth myocytes synthesize growth factors, cytokines, and chemokines,
as well as lipid mediators, in addition to receptors, ion carriers, enzymes, and
constituents of the extracellular matrix (Table
8.5
).
Airway remodeling relies on changes in phenotype of airway smooth myocytes
and fibroblasts, especially in asthma. Mitogens are released by epithelial cells, fi-
broblasts, smooth myocytes, mastocytes, and eosinophils. In addition to mechanical
stress, several growth factors can be involved in the change in aSMC phenotype,
such as epidermal (EGF), fibroblast (FGF2), and platelet-derived (PDGF) growth
factors.
8.4.4.1
G-Protein-Coupled Receptors
In humans, airway smooth myocytes are endowed with multiple types (
350 [
721
])
of G-protein-coupled receptors that participate in the intra-, auto-, juxta-, and
paracrine regulation. Furthermore, alternative splicing diversifies the recepterome
and augments the number of GPCR types encountered on their surface, hence
heterogeneity in GPCR signaling. More than 190 GPCRs have, on average,
>
22
In skeletal myocytes, membrane depolarization activates Ca
V
channels for Ca
2
+
influx from the
extracellular medium. Newly imported Ca
2
+
opens RyR1 ryanodine receptors (voltage-mediated
Ca
2
+
-induced Ca
2
+
release). In cardiomyocytes, Ca
V
channels activated by depolarization carry a
small amount of extracellular Ca
2
+
that, nonetheless, causes RyR2 opening and subsequent large
Ca
2
+
from the sarcoplasmic reticulum.
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