Human Cell Biology and Physiology

1. Human Cell Biology and Physiology Timothy Billington PhD

2. LET’S MUSCLE in on WEEK 4 (27 Oct)

3. MUSCLE CELLS (fibres) 1. Enormous compared with the cells we have seen so far fibres in the thigh are 0.1 mm wide and up to 30 cm long! 2. Multinucleate. (>100 nuclei) with the nuclei lying very close to the cell membrane. Genes in these nuclei control production of structural and catalytic (enzyme) proteins required for muscle contraction. The more copies of these genes, the faster those proteins can be produced 3. Membrane of a muscle fibre has a Transmembrane Electrical Potential (Voltage) due to the uneven distribution of +veand –vecharges across the membrane. A sudden change in transmembrane potential is what initiates a contraction.

4. 4. Inside each muscle cell there are many hundreds of Myofibrils, running the length of the cell. Each myofibril is packed with Myofilaments, made of Actin and Myosin proteins

5. Muscle cells ----- short section of 10 cells lying side-by-side nucleus

6. PART of an INDIVIDUAL MUSCLE CELL Myofilaments, made of Actin and Myosin linear proteins

7. } In a contraction: The Myosin filament stays still and draws the Actin filaments in from both sides SARCOMERE ACTINMYOSIN ACTIN (thin filament) (thick filaments)(thin filament)

8. Myofibrils are each composed of 10,000 Sarcomeres, arranged end-to-end } In a contraction: The myosin filament stays still and draws the actin filaments in from both sides SARCOMERE Sarcomeres are the smallest functional units of the muscle cell. They are about 2micrometres long

9. Contraction of skeletal muscle fibres Myofibrils are able to actively shorten and are responsible for muscle fibre contraction. Actin filaments slide over the fixedMyosin filaments. Mechanism: At each end of the muscle cell, the myofibrils are firmly anchored to the inner surface of the sarcolemma (cell membrane) In turn, the outer surface of the sarcolemma is attached to the collagen fibres of the tendon. Result? When the myofibrils contract, the ENTIRE cell shortens and pulls on the tendon Muscle moves a joint

10. SLIDING FILAMENTS and MUSCLE CONTRACTION SARCOMERE At rest Contracted Notice how the Myosin filaments stay still and the Actin filaments move in from either side Actin Myosin

11. We now know which parts of the muscle cell contract. Want to know: what event initiates a contraction? Answer: An electrical impulse delivered by a motor nerve So how does this happen?

12. TheMOTOR CORTEX of the brain sends an impulse which travels the length of the nerve pathway. From brain to spine to leg muscle for example. nerve pathway via the spine leg Motor Cortex

13. Neuro-Muscular Junction This is the point where the nerve interacts with an individual muscle cell NMJ LEG MUSCLE cell NERVE

14. At the NMJ Nerve releases a neurotransmitter called Acetyl Choline (ACh) ACharrives at the Sarcolemmaand causes the release of Calcium ions ( Ca ++) Ca++, in the presence of ATP, then cause the Sarcomere to contract Contractionwill then continuewhile there is sufficient ATP available and while there are stillimpulses arriving at the NMJ

15. Impulse via a motor nerve Nerve end NMJ sarcolemma AChAChACh ATP ATP Calcium ions released Sarcomere contraction

16. MUSCLE CELL TERMINOLOGY Sarcolemma = muscle cell membrane Sarcoplasm = muscle cell cytoplasm Sarcoplasmic reticulum = rough endoplasmic reticulum Sarcomere = smallest functional unit of a muscle cell Sarcoplasmic reticulum is like a lacy network which surrounds each myofibril for its entire length In the sarcoplasm , in between the myofibrils and the sarcolemma, are hundreds of mitochondria Question:Why is it necessary to have hundreds of mitochondria per muscle cell?

17. We now move on to our new cellular topic

18. CELLS in the NERVOUS SYSTEM • This system includes all the neural tissue in the body • Functional unit? a cell called a Neuron [NEW-RON] • What functions do Neurons have? • Communication • Information processing • Control

19. In the nervous system there are also cells called Neuroglia, which far out-number the neurons Newro-glee-ah Functions of neuroglial cells 1. support the neurons to survive and function optimally 2. separate & protect neurons 3.are a supportive framework for neural tissue 4. regulate the ionic composition of interstitial fluid which surrounds the neurons

20. Let’s see what a typical NEURON looks like dendrites nucleus axon axon terminals sheath cell body

21. Cell body contains a prominent Nucleus Cytoplasm surrounding the nucleus is known as the PERIKARYON In the perikaryon are organelles responsible for energy generation and protein synthesis. mitochondria rough endoplasmic reticulum Perikaryon also contains organelles which synthesise Neurotransmitters, pivotal for cell-to-cell communication Grey matter of the brain is composed of neurons which have large clusters of RER and free ribosomes clusters are so dense that they appear as grey regions

22. Now for some new definitions DENDRITES: Slender, sensitive, highly branched processes extending from the cell body. Active in intercellular communication

23. AXON:Long cytoplasmic process capable of propagating electrical impulses [ Action Potentials ] Conducts electrical impulses away from cell body Transmits information to other nerve cells, or to muscles Makes electrical contact with other cells at junctions called SYNAPSES Some single axons are over a metre long, as for example the sciatic nerve axon which runs from the lumbar region of the spine to the big toe INPUT OUTPUT axon

24. NEURON – NEURON COMMUNICATION The axon terminals of Cell A interact with dendrites of Cell B at a SYNAPSE A B

25. SO, WHAT DOES a SYNAPSE LOOK LIKE?

26. SYNAPSE: Junction between 2 nerve cells or between a nerve cell and a muscle cell. A minute gap across which impulses jump by the diffusion of a neurotransmitter ACh SIGH- NAPS Impulse (Action Potential) Synaptic Gap Axon ACh Receptor Axon terminal Dendrite Neurotransmitter molecules (ACh)

27. SEQUENCE OF EVENTS AT A CHOLINERGIC SYNAPSE [A cholinergic synapse is one where the neurotransmitter is Acetyl Choline (ACh)] Action Potentialarrives, from a cell body, along an axon and then depolarizes the Axon Terminal membrane (pre-synaptic membrane) Extracellular Calcium ions now enter the Axon Terminal and ACh molecules begin to leak into the synaptic gap and diffuse across it, towards the post-synaptic membrane

28. SEQUENCE OF EVENTS AT A CHOLINERGIC SYNAPSE [A cholinergic synapse is one where the neurotransmitter is Acetyl Choline (ACh)] 3. ACh molecules bind to specific receptors on the post-synaptic membrane and this causes a depolarizing of that membrane. Na rushes in and another Action Potential is generated and ? Propagated 4. ACh is then removed by Acetyl Choline Esterase, an enzyme which occupies the synaptic gap. Ach is degraded to Acetate and Choline. Choline is reabsorbed into the axon terminal. Acetate diffuses away into the bloodstream nearby.

29. A synapse between a neuron and a muscle cell is a Neuromuscular Junction (NMJ) Each axon terminal contains mitochondria ( guess why?) and thousands of vesicles filled with neurotransmitter molecules ( Acetyl choline, ACh) The membrane of an axon terminal is the pre-synaptic membrane The membrane of a dendrite is the post-synaptic membrane

30. MYELIN SHEATH: Composed of lipid-rich flat cells which wrap themselves around Axons Electrically insulate axons Causes such wrapped axons to appear white. (White matter in the brain) Cross-section Sheath Axon (end-on) Un-myelinated axons appear grey

31. TRANSMEMBRANE POTENTIAL: As you have learned, ALL cells at rest have an electrical potential difference between inside and outside. Remember: the inside of a cell is negatively charged Neurons are no exception. All neural activities begin with a suddenchange in Resting Transmembrane Potential

32. If that change is BIG enough, we get an ACTION POTENTIAL being initiated Action Potential is a self-sustaining voltage change that propagates along a whole axon membrane, from Cell Body all the way to the nearest Synapse

33. ACTION POTENTIAL:Here is a plot of membrane voltage vs time Depolarizing Repolarizing Hyperpolarizing 1 millisecond

34. Depolarization: Caused by Na channel gates opening which lets Na+ ions rush into the cytoplasm from the outside Transmembrane voltage increases from -70 to +30 m V At peak voltage (+30 m V), Na channel gates now snapshut and……………. Repolarization: begins. K channel gates now openand K leaves the cytoplasm and goes to the outside. Transmembrane voltage begins to drop and goes negative Hyperpolarization:K channel gates now close. Na and K channels return to their resting state ( -70 m V)

35. Question: What is the magnitude of the voltage change when depolarisation of the membrane takes place ? Question: At peak voltage, the cytoplasm of the neuron is full of Na+ ions. The Na+ channel gates now snap shut. How do the Na+ ions then leave the cell so that the resting state returns? Question: When the transmembrane voltage has returned to the resting state, what is the status of K+ and Na+ ions in the cell and in the extracellular fluid? END WK4