Smooth Muscle

Question 1

Smooth muscle functions

Answer 1

. Propels contents through hollow organ tube
. Maintains pressure against contents w/in hollow organ or tube
. Regulates internal flow of contents by changing tube diameter (resistance)

Question 2

Basal tone of smooth muscle

Answer 2

. Low level contraction in absence of extrinsic factors
. Intrinsic property of smooth muscle
. Cytosolic Ca sufficient to maintain low level of cross-bridge cycling

Question 3

Phasic contractions in smooth muscle

Answer 3

. Brief stimulus causes rapid production of force and subsequent rapid relaxation as Ca returns to basal levels
. Occurs in GI tract and urogenital organs

Question 4

Tonic contractions in smooth muscle

Answer 4

. Continuous production of force in presence of falling Ca that remain above basal levels
. Cross-bridge cycling occurs at low level
. Smooth muscles of airways of lungs, all blood vessels, and GI sphincters have tonic contractions

Question 5

Smooth muscle structure

Answer 5

. Sarcomere-like units 
. No t-tubules, troponin
. Less SR 
. Has myosin and actin 
. Regulation of cross-bridge occurs on thick myosin filament

Question 6

Smooth muscle cross bridge cycling pathway

Answer 6

. Inc. cytosolic Ca
. Ca binds to calmodulin
. Ca-calmodulin complex binds/activates MLCK
. MLCK w/ ATP phosphorylates 2 regulatory MLC
. this enhances ATPase activity of myosin which then forms cross-bridges w/ actin
. Cross-bridge cycle maintained as long as Ca remains elevated and Ca-CM-MLCK is activated
. Cycling ends by reduced Ca-dependent activation of MLCP that de-phosphorylates MLC, dec. cross-bridge formation rate

Question 7

T/F The ATP that phosphorylates MLC is distinct from the one hydrolyzed by myosin for cross-bridge cycling

Answer 7

T

Question 8

Latch state in smooth muscle

Answer 8

. Dephosphorylation by MLCP slows cycling creating this state while some other cross-bridges are still attached

Question 9

What plays a major role in inc. cytosolic Ca concentration in smooth muscle? how does it inc. the concentration?

Answer 9

. Extracellular Ca
. Influx extracellular Ca into cell induces release of additional Ca from SR (Ca-induced Ca release)
. Small amt extracellular Ca can result in large inc. intracellular Ca from this induced released

Question 10

Extracellular Ca can enter smooth muscle through _____

Answer 10

. Voltage-gated Ca channels
. Ligand (second messenger) gated Ca channels
. Receptor-gated Ca channels
. Stretch-activated Ca channels

Question 11

What controls smooth muscle tone, contraction and relaxation?

Answer 11

. ANS
. Hormones
. Local paracrine agents

Question 12

Smooth muscles can exhibit what kinds of potentials?

Answer 12

. APs
. Slow-wave
. Oscillations of resting membrane potentials

Question 13

Action potentials in smooth muscle

Answer 13

. Can be simple spike, spike followed by plateau, or series of spikes on top of slow waves of membrane potential
. Only single units fire APs, multi-units don’t
. Ca-dependent not Na dependent
. Activation of VG Ca channels inc sarcolemma depolarize cell and also trigger contraction by inc. intracellular Ca
. Inc. in intracellular Ca responsible for tension summation that results from inc. firing rate of APs
. APs DONT SUMMATE

Question 14

Pacemaker potential

Answer 14

. Spontaneous depolarization of single-unit smooth muscle cells
. Membrane potential gradually depolarizes until it reaches threshold for firing single AP
. Spontaneous depolarization occurs from activation of small cationic current (mostly Na)
.

Question 15

Slow wave potential

Answer 15

. Spontaneous depolarization of single-unit smooth muscle
. Membrane potential slowly oscillates, alternating small depolarizations and slow hyperpolarizations
. When threshold potential is reached the cell fires a burst of APs
. Result from interplay of voltage-dependent Ca channels and Ca-activated K channels

Question 16

Resting membrane potential in smooth muscle

Answer 16

. Not constant, ranges from -65 to -45 mV

. Determined by Na and K fluxes

Question 17

How does smooth muscle contract despite being unable to generate an AP?

Answer 17

. Depolarization of resting membrane potential w/o generating an AP
. Leads to activation of few VG Ca channels (less than those required to trigger AP)
. Intracellular Ca inc. and force of contraction inc.
. Hyperpolarziation of resting membrane potential can lead to closing of VG Ca channels, intracellular Ca dec. and force of contraction dec.

Question 18

Receptor-operated channels in smooth muscle

Answer 18

. Coupled (directly or indirectly) to to voltage-independent channels which then open resulting in a voltage change (de/hyperpolarization)
. Change in membrane potential alters cytosolic Ca
. Same neurotransmitter may produce opposite effects in different smooth muscle

Question 19

Pharmaco-mechanical coupling

Answer 19

. Agonist (hormone/neurotransmitter) binds to its receptor and inc. or dec. cytosolic Ca through second messenger
. Does this w/o changing membrane potential

Question 20

Mechano-mechanical coupling

Answer 20

. Stretch activated channels (mixed cation channels) open when smooth muscle cell membrane is distorted by stretch of an organ
. Resulting depolarization inc. cytosolic Ca
. Contraction opposes the stretch felt

Question 21

Relaxation of smooth muscle

Answer 21

. Dec. in contractile force occurs when intracellular Ca dec.
. Dec. Ca from return of Ca into SR by Ca-ATPase, extrusion of Ca out of smooth muscle cell by sarcolemmal Na/Ca exchanger or sarcolemmal ATPase
. MLCK returns to inactive form
. Enzyme myosin phosphatase removes phosphate from myosin
. Cross-bridge reattachment is inhibited

Question 22

Sarcolemmal Na/Ca exchanger

Answer 22

. Energy for extrusion of Ca against its concentration gradient comes from inward driving force for Na
. Na/K ATPase maintains Na gradient

Question 23

Ca antagonist effect on smooth muscles

Answer 23

. Block voltage-dependent Ca channels
. Reduce Ca influx and Ca-induced Ca release
. Nifedipine, verapamil, diltiazem

Question 24

K channel opener drug effect on smooth muscle

Answer 24

. Cause hyperpolarization of smooth muscle cell s
. Promotes relaxation of muscle and vasodilation of peripheral vascular smooth muscle
. Pinacidil

Question 25

NO in smooth muscle

Answer 25

. Regulates vascular smooth muscle tone and bp
. Many vasodilators produce NO as a signaling molecule in cardiovascular system
. Produced by stimulating enzyme nitric oxide synthase or the NO-cyclic GMP pathway
. Results in inc. cGMP concentrations in cytosol
.cGMP relaxes smooth muscle bc it activates PKG which phosphorylates MLCK inactivating it
.

Question 26

Phosphodiesterase inhibitors

Answer 26

. Inhibit PDES
. Vasodilator
. Enzyme normally converts cGMP into GMP dec. activity of PKG terminating vasodilation
. W/ inhibitor the PKG activity remains elevated for longer time so vasodilation is prolonged
. Viagra

Question 27

Single unit smooth muscle group characteristics

Answer 27

. Electrical coupling: functional syncytium via gap junctions
. Phasic contractions (superimposed on basal tone)
. Spontaneously active from pacemaker cells or enteric nervous system
. Stretch-initiated contraction and relaxation common
. Extrinsic factors modulate ongoing phasic contractions, may alter basal tone
. Seen in GI, ureter, bladder, uterus, small diameter blood vessels

Question 28

Multi-unit smooth muscle characteristics

Answer 28

. Very little electrical coupling, each cell independent of neighbor
. Tonic contractions
. Controlled by extrinsic factors (ANS, hormones, paracrines)
. Stretch contraction/relaxation not common
. Seen in larger diameter blood vessels, lung airways, eye muscles, piloerector mm. In skin

Question 29

Shortening velocity as function of load in smooth muscle

Answer 29

All muscles types generate faster isotonic contractions as load decreases
. Very steep in fast skeletal, fairly steep in slow skeletal
. In smooth, shortening velocity is always very small and only depends slightly on load at very low values