Smooth Muscle Flashcards
Smooth Muscle
Many different kinds with different functions and contraction/relaxation properties
o Contraction and relaxation is ____ in comparison to striated muscle
o Shortening velocities and ATP consumption ____
o Cross bridge cycling rates _______ as well as the number that are active
very slow
low
regulated
Smooth Muscle
Ultrastructural features
Absence of troponin
o Relative abundance of actin, about 2/3 of which is not associated with myosin
but rather is an integral part of the cytoarchitecture
o Absence of transverse tubules
o Paucity of sarcoplasmic reticulum
o The spread nature of the contractile machinery permits contraction over a wide
range
o Single
o Single unit or multi-unit groups: of smooth muscle
Single unit
• Rhythmical activity dependent on myogenic activity
§ Multiunit
• Cells remain quiescent until some incoming signal
• Allows fine motor control
Excitation of smooth muscle types
o Electrical
o Pharmacological/hormonal
o Mechanical
Describe Excitation of smooth muscle
o Electrical
o Pharmacological/hormonal
o Mechanical
§ ANS innveration
§ Commonly cell-to-cell junctions; sometimes inherent, spontaneous ‘pacemaker’ behaviour of the RMP
§ Various neurotransmitter and hormonal agents cause sarcolemmal
depolarisation or increase the conductance of selected ion channels
§ Stretch activated membrane channels
smooth muscle
Types of Action Potentials
o APs highly variable and not always needed to initiate contraction (C & D)
o AP can be associated with twitches and summate to increase force (A)
o Some show periodic oscillations in 𝐸m (NaK ATPase) and trigger APs (B)
o Some pharmacological agents trigger contraction via 2nd messengers & IP3 (D)
smooth muscle
Types of initiating Action Potentials
Spontaneously active
§ Contract rhythmically
Electrically inexcitable
§ SM that don’t produce APs (bronchial, tracheal)
Intermediate
§ Most widely distributed (iris, piloerector, blood vessels)
- Excitation-Contraction Coupling in smooth muscle
Chemical messenger hypothesis
Occurs (as in striated muscle) primarily via Ca2+
o SL depolarisation results in activation of
o Sources of Ca2+:
§ (i) voltage
Both IP3 and DG are involved in a cascade of events beginning with the
activation of a sarcolemmal receptor and finishing in a ‘pulse’ of Ca2+:
Activation of contraction
Both IP3 and DG are involved in a cascade of events beginning with the
activation of a sarcolemmal receptor and culminating in a ‘pulse’ of Ca2+:
i) hormonal or electrical activation of muscarinic, histaminergic or 𝛼-
adrenergic receptors on the sarcolemma
§ (ii) involvement of a membrane bound G-protein in activation of the
enzyme phospholipase C which hydrolyses phosphatidylinositol,
located on the cytoplasmic face of the sarcolemma, into DG and IP3
§ (iii) DG activates PKC which, in turn, phosphorylates Ca2+ channels
and G proteins
§ (iv) IP3 diffuses to the SR or sub-sarcolemmal tubular network where it
binds to a receptor to cause release of Ca2+
There is a ubiquitous (evrywhere) cytoplasmic protein ___________(which is rather
like parvalbumin in skeletal muscle) that can bind Ca2+ in a 4:1 molar
ratio
calmodulin
This exposes the catalytic site on MLCK allowing it to
phosphorylate the regulatory light chain of myosin.
Caldesmon
A Ca2+/calmodulin binding protein known as caldesmon
modulates thin filament interaction
Contraction
§ Fast Cross Bridge Cycling
• Occurs when
a 2nd ATP binds to the myosin head hydrolysing to
myosin-ADP-Pi (as in skeletal muscle) and causing the power
stroke
• Multiple cross bridge cycles can occur, each with an ATP
hydrolysis following a single myosin light chain
phosphorylation
• Fast cycling and shortening occur when MLCK:Phosphatase C
activity ratio is high
Regulation and slow cross bridge cycling
Calcium stimulated myosin phosphorylation is obligatory for the
initiation of cross-bridge cycling with actin
• A special crossbridge state exists allowing smooth muscle to?
maintain tone (force) with minimal ATP expenditure
• If myosin light chains are dephosphorylated, myosin ATPase
activity decreases, making it harder to release myosin heads
from actin
• Attached myosin heads can hold force (“latch” state)
• A non-cycling or slowly cycling complex (AM) is postulated to
explain the “latch” state
• Unloaded shortening velocities vary with relative sizes of the
populations of phosphorylated cross-bridges and “latch-bridges”
• If myosin light chains are ______, myosin ATPase
activity decreases, making it harder to release myosin heads
from actin
dephosphorylated
allowing “latch” state
Time course of events in activation
o Phasic contraction:?
o Tonic contraction?
§ [𝐶𝑎]i phosphorylation and force reach a peak and return to baseline
§ [𝐶𝑎]i and cross bridge phosphorylation decline after an initial spike
but do not return to baseline. Force is sustained at a high level (latch
state)
