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University of Waterloo
BIOL 273
Norman Scott

MODULE ONE Introduction Physiology –1) is integrative; a change in environment or in demand elicits adjustments to many systems. The adjustments are coordinated in order to maximize the outcome. 2) Physiology is the study of function. A) the intention or purpose of an organ or system B) the processes used in an organ or system (muscle contraction, etc.) HOW DOES IT WORK 3) The concept of homeostasis is central to physiology. The internal environment of the body’s cells is kept more or less constant. Most internal variables are regulated, and maintained close to a ‘set-point.’ Methods of Communication Between Cells – 1) Nervous System (fast) 2) Endocrine System (slower) The Resting Membrane Potential The cytoplasm of nerve cells (veurons) has a negative charge with respect to the surrounding extracellular fluid (ECF) (Interstitial fluid/Plasma). This is caused by an asymmetrical distribution of ions between the two components. Basically, the composition of socium, potassium, chloride, bicarbonate, and other anions, etc. amongst plasma, interstitial fluid, and intracellular fluid. Calcium/Chloride/Sodium- high concentration outside in extra fluid, low inside Potassium/Metabolites – high concentration inside in cytoplasm, low outside This distribution is maintained by two factors: 1) Sodium and Potassium are actively transported across the cell membrane. 2) Sodium and Cloride and Potassium ions can cross the membrane, but at different rates (harder for large organic molecules like metabolites) Neuron RMP - -70mV Scenario One – Only potassium(+) can cross: they diffuse out of the cell, down their concentration gradient, until equilibrium is reached. In this scenario, the membrane potential would be based solely on the relative concentrations of potassium ions inside and outside the cell (equilibrium). Use the Nernst Equation to calculate the equilibrium (-90mv) Two – only sodium(+) can cross; they diffuse into the cell, down their concentration gradient, until equilibrium is reached. In this scenario, the membrane potential would be based solely on the relative concentrations of the sodium ions inside and outside the cell (equilibrium at +60mV) Three – only chloride(-) can cross; they diffuse into the cell, down their concentration gradient, until the equilibrium is reached. In this scenario, the membrane potential would be based solely on the relative concentrations of chloride inside and outside the cell. In reality, all three types can cross, but not at equal rates. 1) Potassium can move fastest (greatest influence on voltage, why it’s equilibrium is so close to the RMP) 2) Sodium about forty times slower. 3) The resting potential is at the equilibrium potential of chloride and so there is no movement. Use the Goldman Equation to measure all three equilibrium at once. TWO WAYS OF MOVING: 1) Leak Channels 2) Active Transport; in a resting neuron, the passive leakage of potassium and sodium ions down their concentration gradients is exactly balanced by active transport in the opposite direction. The ions that are responsible for the RMP are distributed on the inner and outer surfaces of the nerve cells. The electrical signals that neurons transmit are disruptions of the RMP. THE BODY IS ELECTRICALLY NEUTRAL. The Graded Potential Neuron – membranes contain channels for potassium, sodium, chloride and calcium. A change in one type of channel, either (closed to open or reverse), changes the distribution of its ions. The electrical potential that is measured across the membrane then ceases to be a RMP. The movement of only a small number of ions can produce a large change in the MP. TWO TYPES of electric signal – Graded/Action. Graded – 1) Depolarizing (MP becomes less negative than -70) 2) Hyperpolarizing (MP becomes more negative than -70), depending on the channel) All depends on intensity and number of ion channels that change. Ligand – something dissolved in the fluid – molecule, ion, etc. More ligand channel, more binding, etc. 1) Depolarizing GP – the ligand gated channel for sodium ions commonly found in the neuronal membranes are closed in the resting state. These channels open for a short time when they bind to their ligan. The result is a temporary increase in the rate of flow through the membrane of sodium into the cell, down their concentration gradient and down their electrical gradient. The number of sodium ions that enter the neuron depends on the amount of ligand that is bound to the channels. The inward flow of sodium ions causes a reduction in the membrane’s polarity at that point, a depolarizing graded potential, which spreads outward across the membrane’s surface. The wave of depolarization decreases in amplitude as it moves. 2) Hyperpolarizing GP – ligand gated channels for potassium. The potassium flood out of the cell, making the membrane more negative. 3) GPs arise on the dendrites or the cell body. The Action Potential 1) The amplitude of AP in a single neuron is not graded, but always the same; typically, a change in the membrane potential of 100mV (from -70 to +30) 2) AP amplitude do not decrease as they travel across a neuron’s membrane, making them suitable for long-distance signal transmission 3) Voltage-gated channels for sodium and potassium ions are responsible for action potentials. They open when the resting membrane is depolarized to a threshold of -55mv. Voltage Gated Channels – sodium and potassium – both open in response to supra-threshold depolarization, but at dif times – Sodium – open instantly, Potassium – after about half a millisecond Each Sodium one has two gates, in the RM, the activation gate is closed, it opens when the threshold is reached. In the RM, the inactivation gate is open. It closes about half a millisecond after the activation gate opens, and cannot be reopened until a few milliseconds have passed and the membrane has repolarized. Sequence of Events 1) At rest, both VG channels are closed. 2) A GP depolarizes the membrane, until 3) The threshold value of -55mv is reached. The VG Na channels at this location immediately open, and sodium ions flood into the cell. 4) Inward movement of NA causes large, rapid depolarization of the membrane. 5) At its peak, the MP reaches +30, The NA channels then start to become inactivated, and NA can no longer pass through them. At the same time, K VG channels begin to open. 6) Allowing K to flow out of the cell, causing the membrane to repolarize 7) To a value slightly more negative than the RMP. The VG Potassium close 8) Over the next few milliseconds, the MP returns to resting value. A rolling wave of static event, depolarization. The amplitude does not depend on the size of the intiating event (as long as it surpasses the threshold, but on two constant factors: 1) The RMP 2) The length of time that the NA channels are open The Refractory Period – make the neuronal membrane much less responsive to stimulation immediately after an action potential has begun. No new AP can start in the absolute refractory period (NA either open or inactivated, the rate cannot be increased, no new AP). After this, there is relative refractory period, in which an AP can start, but only with something really strong (NA go back to rest, K are still open) Trigger Zone – APs created here, at the base of the axon (at cell body) or base of the dendrites. Centre of integration. Only a GP that DEP the membrane to the threshold can generate an AP. If the AMP of GP is below the threshold when it reaches the TZ, no AP (if it is, then AP generated). Summation of GP – two depolarizing GP, neither of which exceeds the threshold can summate and elicit an AP. This is called temporal summation if they arise on the same dendrite, close together in time. IF they arise on different dendrites, it is called spatial summation. A DEP and HYP GP can summate and cancel each other. Coding – a DEP of the TZ membrane that greatly exceeds the threshold, leads to the formation of a volley of APs. The number of APs athat are generated per unit of time indicates the strength of the original stimulus. This is important since the amplitude of all action potentials is the same, no matter what the stimulus strength. Conduction Velocity – APs must be quick, but process of channels are slow. Two Problems with Cytoplasmic Transmission of Signals: 1) Space: large complex animals cannot have that many large thick axons. 2)Although an electrical signal moves faster through the cytoplasm, it loses amplitude as it travels. It is the resting membrane potential and the influx of sodium ions from the interstitial fluid that keep the amp of APs constant. Myelin prevent interchange of ions in the cyto and the fluid. The AP is forced to travel through the cyto, transmission in myelinatied axons of small diameters is fast. Nodes of Ranvier have high concentrations of VG channels, they restore the original AMP of the AP. Saltatory Conduction – conduction down the axon through the nodes of ranvier, the AP leaps from each, it’s a trade – off, the axon covered my MYE, the depolar travels quick, but its amplitude decline. At the Nodes of Ranvier, the AP is restored. How are Signals Tranmitted b/w Cells? Joined by gap junctions – they are electrical synapses where they can pass through holes from each, but no modifying of signals. Most! Do Chemical synapse: 1) AP along the axon, arrives at the axon terminal 2) VG Calcium channels open in the ATerminal, the Ap sweeps over them, allowing calcium to enter the cell 3) The rise in CA inside causes release of NT stored in vescicles 4) NT diffuses across the fluid and binds with receptors (ligand channels) in other membrane, leads to a hyper or depolar GP in the postsynaptic cell Depolarizing GP – arises on Post cell, called Excitatory Postsynaptic Potential (EPSP) Hyperpolarizing GP – called an Inhibitory Postsynaptic Potential (IPSP) These are only for limited time Any factor that decreases the amount of free NT reduced the number of NT bound receptors: 1) Diffusion out of the cleft 2) Degradation by enzymes in the cleft 3) Uptake by glial cells or reuptake by the pre-cell Only one type of NT released from one Synapse, only one type of receptor on Post- cell, at each synapse, only one type of GP can be produced. Neuron can have thousands of synapses. \ Post-Membrane – on a dendrite Pre- Membrane – on an axon. EPSP enhances signal, IPSP reduce. This allows the bidirectional exchange of information. Pre – AP into chemical signals Post – chemical signals into GP Peptide NTs are synthesized in the cell body of the pre-neuron. Vescicles bind to motor proteins called kinesins, which move down microtubules from the cell body to the axon terminal. This fast axonal transport depends on ATP. Glial Cells – Schwann, lots of kinds. Outnumber neurons in CNS Functions: 1) Support and nourish neurons 3) Assist in directing them during development establishment of correct synapses 4) Act as immune cells 5) Form Myelin 6) Uptake of NTs Organization of the CNS CNS – brain and the spinal cord, receives the processes incoming (sensory info about the environment). Sends appropriate signals to effector organs: skeletal muscles, smoother muscle, heart, digestive organs, some endocrine glands. Consists of afferent (to the brain) and efferent (to the body) neurons. Efferent – 1) somatic motor division carries signals to the skeletal muscles 2) Autonomic division carries signals to all other effector organs: 1) Sympathetic Branch
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