Excitable tissue, muscle lecture; 4

Question 1

What are some examples of where smooth muscle is found?

Answer 1

• Blood vessels
• Airways
• Bladder and reproductive organs
• Iris and ciliary muscles

Question 2

Describe the smooth muscle: single unit vs multi unit

Answer 2

Single Unit: sheets of cells that are electrically coupled and act in unison i.e. as one unit - often spontaneously active. Found in most blood vessels and hollow organs (respiratory, digestive, urinary and reproductive tracts)

Multiunit: tissue made of discrete bundles of independent cells which are densely innervated and contract only in response to its innervation (e.g., vas deferens, iris, piloerectors)

Question 3

Describe the basic structure of smooth muscle:

Answer 3

Spindle shape, 5 μm wide, 100-400 μm long with central nuclei

Question 4

Describe the basic cellular structure of smooth muscle: (think of the ways it is different to skeletal and cardiac msucle.

Answer 4

• No T-tubules – caveolae instead (act to increase surface area)
• Dense bodies act like z-lines to “anchor” actin to sarcolemma
• In unitary smooth muscle cells gap junctions electrically connect the cells together
• Intermediate filament is cytoskeleton element
• Poorly developed SR

Question 5

Describe the contractile units of smooth muscle:

Answer 5

No striations, but contains actin and myosin filaments. i.e no sarcomere units, but has the contractile filaments

Less organized – actually allows for greater shortening: Can operate over large range of lengths (60 - 75% shortening possible)

Question 6

How is smooth muscle contraction initiated?

• Primary ions
• Trigger
• Sorts of neural stimuli

Answer 6

Electrical behaviour very complex but primarily due to voltage gated Ca2+ channels (relatively few Na+ channels)

Trigger for contraction is an increase in intracellular calcium. The Ca2+ entering through channels in the cell membrane is a very important source of calcium (i.e. less reliant on SR stores)

Can be neural, hormonal or spontaneous (myogenic)

Question 7

Describe the Ca regulation of smooth muscles:

Answer 7

Calcium source: Extracellular and SR
Regulation via voltage, hormones, neurotransmitters and specific ions
e.g.
• L-type Ca2+ channel. (voltage gated)
• Receptor operated Ca channel
• Calcium induced calcium release via the RyR in the SR
• Ca ATPase, SERCA pump, NCX

Question 8

Describe how hormones can change SR ca levels

Answer 8

• Hormones (e.g. angiotensin II) or neurotransmitters (e.g.
noradrenaline) acting on G-protein receptors to increase IP3 levels, which act on IP3 mediated calcium release channels in SR

Question 9

Give an overview of the five steps of contraction in smooth muscle:

Answer 9

1. Increased intracellular Ca++
2. Calmodulin (CaM) activation
3. Activation of calmodulin dependent protein kinase (myosin light chain kinase: MLCK)
4. Phosphoralisation of myosin
5. Actin /myosin interaction resulting in contraction

Question 10

Describe step one of contraction in smooth muscle, more detail:

Answer 10

Calcium ions (Ca2+) enter the cytosol from the ECF via voltage- dependent or voltage- independent Ca2+ channels, or from the scant SR.

Question 11

Describe step two of contraction in smooth muscle, more detail:

Answer 11

Ca2+ binds to and activates calmodulin.

Note: in smooth muscle the regulatory protein is
calmodulin, and the troponin complex is absent.

Question 12

Describe step three of contraction in smooth muscle, more detail:

Answer 12

The activated calmodulin then activates myosin light chain kinase (MLCK). MLCK is an enzyme.

Question 13

Describe step four of contraction in smooth muscle, more detail:

Answer 13

MLCK activates the myosin by phosphorylating it, which in turn activates the myosin ATPases.

Question 14

Describe step five of contraction in smooth muscle, more detail:

Answer 14

Activated myosin forms cross bridges with actin of i
the thin filaments and shortening begins in the usual Pi fashion.

Contraction occurs by the same actin-myosin interaction asin striated muscle (sliding filament) , but….. REGULATION IS MYOSIN NOT ACTIN BASED

Question 15

Describe the regulation of the contractile filaments by myosin

Answer 15

Myosin does not hydrolyse ATP (to become energized) unless it is first phosphorylated (on the regulatory light chain, LC20 located on the neck of the myosin)

The enzyme myosin light chain kinase (MLCK) phosphorylates the light chain, in the presence of the activated calmodulin.

Question 16

Is smooth muscle contraction fast?

Answer 16

maximum rate of crossbridge formation is low = slow contractions)

Question 17

What regulates MLCK?

Answer 17

MLCK is active only in the presence of a small Ca-binding protein, calmodulin (and only when it has Ca bound).

Question 18

Describe the smooth muscle relaxation:

Answer 18

Contraction ends when a myosin light chain phosphatase dephosphorylates the myosin light chain.

Ca-ATPase in cytoplasm membrane primary mechanism for reducing intracellular Ca++ .

Smooth muscle contraction is enzyme regulated – slow but efficient!

Question 19

Describe how the myosin light chain kinase (MLCK) and myosin light chain phosphorylation (MLCP)

Answer 19

Increased MLCK activity (Ca2+ regulated) will favour contraction Increased MLCP activity will favour relaxation

When intracellular Ca2+ drop MLCP activity will dominate

Question 20

What are the core features that influence smooth muscle contraction? and what are the factors that directly influence these?

Answer 20

Cytosol Ca
MLCK or MLCP activity

Influenced by:

• Neurotransmitters
• Hormones
• Environment i.e pH
• Histamine
• Adenosine
• Prostacyclin
• Nitric oxide
• Stretch