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Lecture 1-7 NOTES

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University of Toronto Scarborough
Biological Sciences
Joanne Nash

Lecture 1 (slides 11,12,14-24) Homeostasis = a relatively constant internal environment Study of body functions in a disease state = pathophysiology Claude Bernard One of the first physiologists -was around the late 1800’s -- Fluid matrix [extracellular fluid & related fluid in the body] = he’s talking about the fluid within the body. Temperature change or bacteria invasion in the body – we’re still able to cope. - Our bodies allows us to function and carry out our daily tasks. - it does this by maintaining homeostasis. Some of Bernard’s discoveries: - So he showed the mechanism of muscle contraction. [@ curare] - Carbon monoxide – that is why smoking is so bad! Physiology: How the body maintains homeostasis Homeostasis & the mechanism that the body uses to regulate homeostasis: [Fig. 1.3] -Protective layer – which is the skin for us -contained within this protective layer [skin] is loads of fluid Within this fluid are cells – which also contain fluid -homeostasis is the balance between the fluid within the cells compared to the fluid within the protective layer. It’s not like chemical equilibrium – where the body is trying to balance out the two systems or the two fluids so that they are identical.  it’s to make them similar where it allows us to function in a way to detect the changes in movement/smell/sound. -all of our abilities to do that is all to do with changes in homeostasis. @ Fig. 1.2 - Complicated version of Fig. 1.3 - Shows all the diff. Compartments in the body – where although they are essentially different & are compartments – they do interact – e.g. diffusion across barriers/membranes – which allows movement of fluid - The body is not a completely closed system = we have a mouth & a nose! & we also excrete things through barriers/systems within our bodies! - - the ability of different systems to interact in our body – the ones mentioned in the figure! Physiology = Homeostasis; Pathologies arise when homeostasis fails So when homeostasis fails = we get ill/sick! Environment toxins that get into our body - & the body copes with them [sometimes fails] -our bodies can deal with it to a certain extent! so – with something like the examples listed on the slide 1)So the toxin enters the body 2) then there is an internal change 3) which results in a loss of homeostasis 4) Then the organism can compensate [usually] - & we remain healthy. BUT what if that FAILS?! e.g. Glucose – so when a healthy person takes glucose in the form of a chocolate bar. - So they have the chocolate - - they’re fine 1) their body has an increase in glucose 2) Their body changes the salt/ water balance 3) Then insulin is excreted 4) Then the insulin breaks down the glucose – so body returns to homeostasis! - BUT what about a diabetic person - when there is NO INSULIN [so external change] 1) so blood glucose continues to rise 2) It leads to huge changes in the body – changes in salt balance btwn intracellular & extracellular compartments 3) Eventually – what this can cause in a diabetic person [with no insulin] is: slurred speech, fainting, coma, blindness & loss of blood to outer extremities. [this was an example of when the body is NOT able to compensate for the external change – therefore compensation fails = & illness arises] -- What about an INTERNAL CHANGE? - FEVER – causing internal change in body temp. - Concentration of neurotransmitters (e.g. Increase in dopamine = schizophrenia or a decrease = depression) - Cell growth (too much = cancer) - Cell death (too much = neurodegeneration) [e.g. Neuro-degenerative diseases = Parkinson’s & Alzheimer's disease] So how do we understand mammalian physiology? In 2003 -Genome project: thought that once completed – that we could cure & treat ALL diseases -unfortunately – THAT DID NOT OCCUR ! PROBLEMS: 1) It was found that there are fewer genes than proteins in the body: so each gene encodes several proteins [not the only problem discovered] 2) It’s that the diff. Proteins have diff. Functions in diff. Pathways in diff. Cells in diff. Tissues. = so body is extremely complicated  & to really understand how it works right down from the protein level to the organism level = we’ve to take the top down research approach [so going from the organism to the organ to tissues & so on] BUT we also have to think about what the proteins do to the diff. Pathways. = so we also have to take the Bottom up approach as well! 2. Requirement for a Hypothesis Physiologists require a hypothesis to further our understanding of the body. - Hypothesis – although it’s quite artistic in the fact that it’s creative but it can’t be abstract [whereas art can be] – there has to be logic behind it! 3.Experimental design, e.g choice of the correct system (i.e MODEL) As scientists – when designing things – have to take diff. Things in account – with the first one being the choice of model. - Test tube/ Cell Culture : so you can control the diff. Variables within a test tube or a cell culture - & everything that can happen is controlled for – whereas when you use animals or humans – that’s not necessarily always the case. - Understand cellular + molecular mechanisms = to do this is humans/ rats – you would have to take apart the parts to understand the cellular/molecular mechanisms. - Relatively quick - but with humans – it could take years. - [RMR – WE CAN’T DESIGN A PERFECT EXPERIMENT] - Note: physiologically – you won’t use feelings as a measure!` - OVERALL: we NEED to do choose all of these models – so use test tubes – then cell culture – then animals & then move eventually to humans! Lecture 2 –RESTING MEMBRANE POTENTIAL (print slides 3-18) Typical concentration of ions in intracellular (IC) and extracellular (EC) solutions: In Extracellular (EC) Solution: ([]=concentration) - Large [] of sodium ions - High [] of chloride ions - Relatively low [] of potassium ions. BUT in Intracellular (IC) Solution: - High [] of potassium ions - Not so much of chloride or sodium ions -  so the chemical gradient between these 2 compartments exists b/c of the difference in the [] of sodium, potassium and chloride ions between the two compartments. [So EC is high in sodium ions While IC is high in potassium ions] - So it is the [] of sodium ions outside and the [] of potassium ions inside that’s crucial with regards to controlling resting membrane potential and subsequent changes in potential of the membrane. There is a chemical gradient between the IC and EC because of the properties of the plasma membrane that separates them A crucial aspect that controls the distribution of ions between the two compartments is the properties of the PLASMA MEMBRANE. Polar molecules: -can’t pass through the membrane itself (as membrane is non-polar) - Need to pass through (protein) channels Why is there a chemical gradient between the IC and EC? The Na / K ATPase pump located on the cell membrane Transports 3 Na ions out of the cell and simultaneously transports 2 K ions into the cell -> that itself establishes a difference in charge between the 2 compartments -> it’s taking out more +ve ions outside than taking inside Therefore - this ELECTROGENIC pump produces net movement of positive charge outside the cell. Ions pass through the membrane via ion channels The actual mechanisms that control’s RMP - One the crucial things that controls this is the presence of ion channels within the membrane [=these are voltage-gated] - -- - So at rest – the sodium channel is closed! - & a from of potassium channel (2 types of potassium channels) is open = so b/c there is lots of potassium inside the cell -> there is a tendency for the potassium to move out of the cell, down it’s [] gradient! What generates the resting membrane potential (-70mV)? 1. K leak channels So there are three main factors that govern RMP are: + 1) K leak channels 2) Na/K ATPase pump 3) The properties of the plasma membrane *[2) & 3) on next slides]* -- So Na+ & Cl- channels are closed and at rest. - The K+ channels are open! (leak K+ channel = a form of potassium channel open at rest) -- So while the potassium is moving out of the cell – you still have these negatively charged proteins within the cell Negatively charged proteins = are BIG – so they can’t escape the membrane. - So the level of potassium movement is controlled somewhat by the negatively charged proteins. - So, the net negative charge within the cell – > retaining these potassium ions within the cell. Forces controlling the movement of ions between IC and EC compartments - this doesn’t mean that there is an equal [] of ions between the compartments - it’s the balance of electrical charges and the chemical gradient that governs this -you calculate it – you measure it using EQUILIBRIUM POTENTIAL. EQUILIBRIUM POTENTIAL = the time at which there is NO movement of ions between the 2 compartments is when equilibrium potential is reached. -> so – this is the actual voltage that has to be applied inside the cell using recording electrode to prevent movement of ions [only in artificial situations] -the equilibrium potential can only be measured in artificial models! - Or in our bodies – physiologically - we measure this when the cell is permeable to only one ion. - E.g. So if we are interested in potassium equilibrium potential – so that’s when only the K+ channel would be open! Lecture 3 -The Action Potential (1) print slides 3-16,18,19,21 Nerve and muscle cells are excitable cells: Nerve and muscle cells are excitable = meaning they’ve the ability to change in their membrane potential. Remember – there is lots of potassium INSIDE the cell -while there is lots of sodium OUTSIDE the cell. -& the inside of the cell is NEGATIVE to outside of the cell -so when sodium comes in – so that’s movement of positive charge into the cell – that makes the cell more POSITIVE!  & that increases the excitability of the cell = so the movement of sodium into the cell increases the excitability of the cell! -So when potassium moves out of the cell – that causes an increase in the negative charge of the cell (inside the cell) [so that relative increase in the negative charge DECREASES the excitability of the cell!] - & we measure these changes in excitability using electro-physiology equipment discussed in previous lecture! (in picture on the slide) - ->so the electrode placed inside the cell & another placed outside the cell. - & the vol
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