PHSL2101 – Excitable Cells

PHSL2101 – Excitable Cells Contents Lecture 1 ................................................................................................................................................ 2 To describe very generally an example of a single cell function ........................................................ 2 To appreciate cells are basic fundamental units & be able to define what is meant by excitable cells and give some examples ..................................................................................................................... 2 To appreciate single cells use chemical and electrical signalling ....................................................... 2 To schematically draw a cell membrane and to identify the functional components of a typical membrane phospholipid and give an example .................................................................................... 2 To know the terms polar and non-polar and how it relates to membranes and ions ........................... 3 To relate the basic components of an electrical circuit to a potential difference across the cell membrane............................................................................................................................................ 3 Lecture 2 ................................................................................................................................................ 4 To appreciate ions are hydrated in solution. ....................................................................................... 4 To distinguish active and passive membrane transport....................................................................... 4 To distinguish simple and facilitated diffusion, and facilitated diffusion via channels and carriers .. 4 To briefly describe an example of a facilitated diffusion transport process including physiological relevance and protein involved ........................................................................................................... 6 To be able to define ion channels and their basic properties of gating and selectivity ....................... 6 Lecture 3 ................................................................................................................................................ 7 To recognise osmosis as water diffusion and relate tonicity and water flux across cell membranes.. 7 To be able to define primary and secondary active transport, and cotransport and counter-transport, and give examples of each .................................................................................................................. 8 To know the basic cellular function of the Na+ pump and the ions that it transports, including the directions and quantities ..................................................................................................................... 8 To be able to briefly describe exocytosis and endocytosis using physiological examples ................. 9 To understand the forces that dictate how an ion moves across the cell membrane, including being able to describe electrochemical equilibrium and to predict how an ion moves at a given membrane potential and concentration gradient, or at a given equilibrium potential......................................... 10 To know the Nernst equation and be able to use it (if given the values of the constants) to calculate equilibrium potentials ....................................................................................................................... 10 Lecture 4 .............................................................................................................................................. 12 To be able to describe how the resting membrane potential is generated and how changes in membrane potential occur (in terms of ion flows) ............................................................................ 12 Define depolarization, hyperpolarization, electrochemical equilibrium ........................................... 12 To know the basic cellular physiology mechanisms (6 steps) of how pancreatic beta cells secrete insulin and the role of specific membrane transport processes and ion fluxes in this process ......... 13 Lecture 5 .............................................................................................................................................. 15 To understand the physiological mechanisms of the Action Potential, including: ........................... 15 1

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 To be able to briefly describe exocytosis and endocytosis using physiological examples - Exocytosis  From inside the cell to outside (when the cell takes a shat) - Endocytosis  From outside the cell to inside  3 forms:  Phagocytosis (Particles/Food) o Example: WBC swallowing bacteria  Pinocytosis (Water/liquid) o Example: Uptake of water in large intestines through microvilli  Receptor mediated endocytosis (Specific molecules) o Example: Uptake of cholesterol

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 To understand the forces that dictate how an ion moves across the cell membrane, including being able to describe electrochemical equilibrium and to predict how an ion moves at a given membrane potential and concentration gradient, or at a given equilibrium potential - Ions move according to ELECTRICAL and CHEMICAL forces - Electrical force  Opposite charges attract, like charges repel - Chemical force  Diffusion. Ions moving from high to low concentration - At electrochemical equilibrium, there is no ion movement as

- In a cell, the negative resting membrane potential provides an electrical force that favours cation influx and anion efflux (inside cell is negative so cations go there) - In a cell, the concentration gradient provide a chemical gradient for K+ efflux and Na+ influx (lots of K+ inside cell so it want out. Lots of Na+ outside want in)

 To know the Nernst equation and be able to use it (if given the values of the constants) to calculate equilibrium potentials - The Nernst Equation is:

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 

Where,

 x is the ion  z is the valency of the ion species x (e.g. -1 for Cl-)  xout means the extracellular concentration of ion x  xin means the intracellular concentration of ion x - Example question:

  

At resting potential, only the K+ channels are open For K+ ions (at 37oC) NOTE: Assume 37oC because body temp



Using the Nernst equation,



=



≈ −98

× log(

=

× log(

)

)

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Lecture 4  To be able to describe how the resting membrane potential is generated and how changes in membrane potential occur (in terms of ion flows) - A cell at rest has a membrane potential of -70mV. This means that the inside of the cell is negatively charged relative to the outside. This is the RESTING MEMBRANE POTENTIAL. A cell at rest is not receiving or sending signals - Recall: The inside of the cell is mostly K+ - The outside of the cell is mostly Na+ 

These ions wish to move in the direction of their driving forces



K+ want OUT, Na+ want IN

- HOWEVER, most of the Na+ channels are closed 

More K+ leaving cell than Na+ coming in



Results in net outward movement of + ions (the negative resting membrane potential)

- Changes occur in the potential when gated channels open or close, changing membrane permeability of a specific ion

 Define depolarization, hyperpolarization, electrochemical equilibrium - Depolarisation 

When the membrane changes to a more positive potential

- Hyperpolarisation 

When the membrane changes to a more negative potential

- Electrochemical equilibrium 12

 To be able to compare and contrast the broad features of signalling via ionotropic and metabotropic receptors, with an example of each - There are 2 types of receptors: ionotropic and metabotropic - Ionotropic receptor  A receptor that is a ligand-gated ion channel  The binding of a ligand to the receptor opens the channel. Ions flow through the channel and change the membrane potential V m  SELECTIVITY, different receptors for different ligands  Very fast transmission that occurs and terminates rapidly  Example: the nicotinic ACh receptor at the neuromuscular junction above ^.

 - Metabotropic receptor 23

 A receptor that is associated with a G protein (G protein-linked receptor) 

The binding of a ligand to the G protein-linked receptor activates the G protein. There are 2 ways G proteins work:  Direct coupling: The G protein opens or closes an ion channel

  Second messenger system: G protein activates or inhibits an enzyme that produces the second messenger. This messenger either opens or closes an ion channel or elicits some other response from the cell

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