Cell Physiology Objectives: 1. People esta respuesta no la hay en el libro, ni en el handout, por lo tanto sale d mi conocimiento.

Me corrigen si estoy mal. O H H

H-bonds se forman de molcula + a y viceversa. Por lo tanto, NaCl se disociar en Na+ y Cl- y Na+ se juntar con O- y H+ con Cl-. Hidrophobic = repelled from water (hates water) Hidrophilic = dissolves in water (water lover) 2. The cell membrane is composed of a bilayer of phospholipids and proteins. Lipid-soluble substances cross cell membranes (hydrophobic) and watersoluble cannot cross (hydrophilic). There are integral (anchored to and imbedded in) or peripheral (not imbedded) proteins. Fluid mosaic model

3. Reflection coefficient ()= is a dimensionless number ranging between 0-1 that describes ease with which a solute crosses a membrane. = 1 membrane impermeable to the solute and exert its full osmotic effect. = 0 membrane freely permeable to the solute and there will be no effective osmotic pressure differences.

 = 0-1 most solutes are neither impermeable, nor freely permeable and effective osmotic pressure between its maximal possible value and zero. When two solutions separated by a semipermeable membrane have the same effective osmotic pressure they are isotonic; if they have different effective osmotic pressures (EOP), the one with the lower EOP is hypotonic and the one with the higher EOP is hypertonic. Water flow from hypo to hyper.
1.1.4) Contrast the following units used to describe concentration: mM, mEq/l, mg/dl, mg%. List the values and normal range for plasma Na +, K+, H+ (pH), HCO3-, Cl-, Ca2+, and glucose, and the typical intracellular pH and concentration of Na +, K+, Cl-, Ca2+, and HCO3-. Substance and Units Intracellular Fluid Na+ (mEq/L) 14 K+ (mEq/L) 120 Ca2+ , ionized (mEq/L) 1X10-4 Cl- (mEq/L) 10 HCO3- (mEq/L) 10 pH 7.1 Osmolarity (mOsm/L) 290 Glucose (mmol/L) Extracellular Fluid 140 4 2.5 105 24 7.4 290 4-8

1.1.5) Differentiate between the terms osmole, osmolarity, osmolality and tonicity. List the typical values and normal range for plasma osmolarity.

Osmole= unit of measurement that defines the number of moles of a chemical compound that contribute to a solution's osmotic pressure. Osmolarity= is a measure of the osmoles of solute per liter of solution. Osmolality= is a measure of the osmoles of solute per kilogram of solvent. Tonicity= is a measure of effective osmolarity or effective osmolality. Tonicity is a property of a solution in reference to a particular membrane, and is equal to the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across that membrane. Tonicity, also, depends on solute permeability (permeant solutes do not affect tonicity; impermeant solutes do affect tonicity). Tonicity is generally classified in three ranges; hypertonicity, hypotonicity and isotonicity. Normal Plasma Osmolarity= 290 mOsm/L

1.1.6) Understand the difference in free energy concept. The free energy or potential energy is the total amount of energy in a physical system which can be converted to do work. In the cell mebrane the Na +/K+ ATPase creates this free energy in the form of concentration gradient through the hydrolysis of ATP. This concentration gradient (free energy) can be used by secondary active transport, to generate an action potencial, or to depolarize the membrane.

10. Based on the principle of ionic attraction, explain how a potential difference across a membrane will influence the distribution of a cation and an anion. ***Membrane potential is the difference in electrical potential (voltage) between the inside and outside membrane surfaces under resting conditions. If the cell membrane is permeable to an ion, the ion will flow down its electrochemical gradient and attempt to drive the membrane potential toward its equilibrium potential. If the cell membrane is impermeable to an ion, that ion will make little or no contribution to the membrane potential. Depolarization means the membrane potential has become less negative. Depolarization occurs when there is net movement of positive charge into the cell, which is called an inward current. Hyperpolarization means the membrane potential has become more negative, and it occurs when there is net movement of positive charge out of the cell, which is called an outward current. 11. Define the term "steady state" and differentiate it from "equilibrium." Relate the pump-leak model of steady state ion content to cell solute gradients and cell volume maintenance.

According to Costanzo, the "new steady state" is the operating point at which the cardiac and the vascular function curve intersect will have changed (pg. 153). Steady state is a more general situation than dynamic equilibrium. If a system is in steady state, then the recently observed behaviour of the system will continue into the future..In many systems, steady state is not achieved until some time has elapsed after the system is started or initiated. This initial situation is often identified as a transient state, start-up or warm-up period. While a dynamic equilibrium occurs when two or more reversible processes occur at the same rate, and such a system can be said to be in steady state; a system that is in steady state may not necessarily be in a state of dynamic equilibrium, because some of the processes involved are not reversible. Sorry guys..don't know what they mean about the pump-leak model??

12. Differentiate the following terms based on the source of energy driving the process and the molecular pathway for : diffusion, facilitated diffusion, secondary active transport, and primary active transport. Diffusion: is passive transport which involves non-coupled transport of solutes across the plasma membrane due to its concentration difference. The term passive means "no energy is expended directly to mediate the transport process. The net rate of diffusion is measured using the following formula: J=PA(C1-C2) J: rate of diffusion A: membrane area P:permeability and (C1-C2) : concentration difference. Facilitated Diffusion: is the transport of a substrate by a carrier protein down its concentration gradient. This is required for substrates that are not permeable to either the lipid bilayer or ion channels and is faster than simple diffusion. Secondary active transport: AKA coupled transport and this type uses energy of ionic gradients. Coupled transport carries substrates against their concentration gradient, but transport is provided indirectly from the energy stored in the concentration gradient of an additional ion transported in the same cycle. Coupled transporters are also divided into 2 groups: 1. Cotransporters/symporters that move solutes in the same direction and 2. exchangers/antiporters that transport solutes in opposite directions. Primary Active transport: is the transport of a substarte across the plasma membrane against its concentration greadient. It requires the input of cellular energy in the form of ATP. Proteins that mediate this type of transport are known as pumps which use the energy derived from ATP hyudrolysis to power the transport of substrates against their concentration gradient. Example of this pump: Na+/K+ ATPase.
1.1.13 Describe how transport rates of certain molecules and ions are accelerated by specific membrane transport proteins (carrier and channel molecules).

The lipid component of the membrane is responsible for its low permeability to water soluble substances such as ions, glucose, and amino acids . Integral membrane proteins are embedded in and anchored to the membrane by hydrophobic interactions. Carriers and channels are integral proteins. Carrier proteins transport substances across the cell membrane. Carrier mediated transport include facilitated diffusion, primary active transport, and secondary active transport. This type of transport presents three important features related to the binding sites for the solute: Saturation stereospecificity competition

Membrane channels allow polar charged ions to flow across the plasma membrane. The ion move quickly through proteins having pores known as ion channels down its electrochemical gradient. Many channels are active in the resting state of the cell (produce membrane resting potential), but others are gated by perturbations in the membrane. They are controlled by gates and can be activated by voltage or a particular ligand. Ion channels exhibit selectivity based on the size of the channel and the charges lining it. 1.1.14 Describe how energy from ATP hydrolysis is used to transport ions such as Na +, K+, Ca2+, and H+ against their electrochemical differences (e.g., via the Na + pump, sarcoplasmic reticulum Ca2+ pump, and gastric H+ pump).

In active transport, one or more solutes are moved against an electrochemical potential gradient (from low to high concentration). In this process, ATP is hydrolyzed to adenosine diphosphate (ADP) and inorganic phosphate (Pi), releasing energy from the terminal high energy phosphate bond of ATP. When the terminal phosphate is released, it is transferred to the transport protein, initiating a cycle of phosphorylation and dephosphorylation. When the ATP energy source is directly coupled to the transport process, it is called primary active transport. Proteins that mediate primary active transport are known as pumps.

1.1.15 Explain how energy from the Na+ and K+ electrochemical gradients across the plasma membrane can be used to drive the net uphill (against a gradient) movement of other solutes (e.g., Na +/glucose cotransport; Na+/Ca2+ exchange or counter-transport). Apply this principle to predict possible therapies for secretory diarrhea.

Coupled transport carries substances against their concentration gradient, but transport is provided indirectly from the energy stored in the concentration gradient of an additional ion transported in the same cycle. In coupled or secondary active transport, one of the solutes moves down its electrochemical gradient, and the other solute moves against its electrochemical gradient. Metabolic energy, as ATP, is not used directly, but it is supplied indirectly in the concentration gradient across the membrane. The active movement against the concentration gradient uses ATP hydrolysis. This helps maintain the concentration gradient that will help to move the other coupled solutes passively across the membrane. [The most common cause of secretory diarrhea is a cholera toxin that stimulates the secretion of anions, especially chloride ions. Therefore, to maintain a charge balance in the lumen, sodium is carried with it, along with water] (wikipedia). Oral administration of sodium and glucose can help. Those solutes enter the cell from the intestinal lumen using the cotransporter driven by the gradient energy maintained by the primary active transport of sodium and potassium. With sodium entry, water can also be absorbed into the cell, thus preventing dehydration. A treatment could also be focused on the sodium amino acid cotransporter.
[Dehydration remains the major cause of morbidity and mortality in cholera and other diarrheas and any reduction in the fluid loss would certainly be helpful. Initially, intravenous saline therapy was used. Based on physiological principles, it was recently found that oral rehydration was possible, a discovery that is one of the triumphs of modern biomedical research. Provision of sodium with glucose (or substances like rice powder that could be converted to glucose) affords a cheap and easy to administer therapy that prevents dehydration. Fans of medical folklore immediately recognized that boiled rice water has always been the mainstay of treatment of infantile diarrhea in the third world. Similarly, one can also make a strong case for chicken soup, which has a high peptide content that could be hydrolyzed to amino acids and afford large amounts of cotransported solutes for sodium absorption. Before images of sage grandmothers with infinite primal wisdom carry one away, it should be emphasized that only mixtures that contain the appropriate proportions of salts and cotransported solutes reduced the diarrhea-related mortality of infants in poor countries. These discoveries were capitalized on to make the ubiquitous Gatorade and other sports drinks in wealthy countries.]

1.1.16 Describe the role of water channels (aquaporins) in facilitating the movement of water across biological membranes. Aquaporins are integral membrane proteins from a large family of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. Aquaporins selectively conduct water molecules in and out, while preventing the passage of ions and other solutes. Also known as water channels, aquaporins are membrane pore proteins.

Handout

CPO2

1. Hyperkalemia is an example of accommodation. Hyperkalemia elevated serum K+ concentration. At rest nerve and muscle cell membranes are very permeable to K+; an increase in extracellular K+ concentration causes depolarization of the resting membrane potential. Although, the membrane potential is closer to threshold, the cell is LESS likely to fire an action potential b/c this sustained depolarization closes the inactivation gates on Na + channels.

2. Slow opening of the K+ channels increases K+ conductance higher than Na+, resulting in repolarization of the membrane potential. Thus, repolarization is the return of the membrane potential to its original value due to K+ efflux (exiting the cell).

3. When the cell membrane is held at a depolarized level a threshold potential is passed without firing an action potential. Example is hyperkalemia. Cell Physiology COP2 4- What substances block the production of action potential and why? Botulinus Toxin blocks Ach release from presynaptic terminals, causing total blockage of neuromuscular transmission, paralysis of skeletal muscle, and death of respiratory failure Curare Competes with ACh for receptors on motor end plate, causing a decrease in EPP. In maximal doses it causes paralysis and death. Neostigmine AchE inhibitor prevents the degradation of ACh in the synaptic cleft and they prolong and enhances action of ACh at motor end plate. Hemicholinium- blocks reuptake of choline into presynaptic terminal, which depletes ACh stores from presynaptic terminal. 5- Protease application degrades the h-gate of the sodium channel. what will be the action on the time course of the action potential? The h-gate is the inactive sodium gate and so if the protease application degrades it, there will be closed gates ready for activation (m-gates) and the time course will have a smaller refractory period than what it should have causing the action potentials to be more frequent.

6- Could you remember the Nerst Equation for equilibrium potential? E = [RT/zF]* Log [Co/Ci] 7. How is expressed the goldman Hodgkin katz equation? Es una pendeja escribir esa cosa (out of this world), so libro texto p 18. Side, it considers the contribution of each ion by its relative permeability.

8. What is the refractory period? a. Absolute refractory- period during which the cell is resistant to a second potencial ( Na+ voltage gated channels are inactive) b. Relative refractory- some of the inactivated Na+ channels are reset to close available to be opened state, K+ channels are open. (another action potential could e elicited with enough stimulus, but it would not reach the maximum amplitude). 9. Could you explain the changes in Na+ and K+ conductance during action potential? a. Reaching the threshold, Na+ conductance action potential. b. Depolarization= Na+ channels open (activation or m gates). Then, inactivation o H gates closes Na+ conductance. c. Slowly opening of the K+ channels (n gates) K+ conductance ( higher than Na+ conductance) REPOLARIZATION
CP02 multiple Choice Qs

1)D The immediate cause of the resting potential of an axon is the high membrane permeability to K 2)B Hyperkalemia reduces the excitability of neurons and muscles cells because increased extracellular K.. deporalizes the cell, thus inactivating voltage-gated Na chanels 3)B The velocity of an action potential conduction is increases by decreasing effective membrane capacitance (costanzo p. 23) CP03 1) An acetylcholinesterase inhibitor at the neuromuscular junction will prevent the degradation of ACh in the synaptic cleft. Used in the treatment of myasthenia gravis where muscles are weak because there are antibodies to ACh receptors on motor end plates of skeletal muscle. It allows higher levels of ACh to counteract the low levels and allow for a normal end plate potential (depolarization of motor end plate).

2) Ca2+ is needed at neuromuscular junction to in order for the neurotransmitter stored in synaptic vesicles be released by exocytosis into the synaptic cleft. This Ca2+ is obtained from ECF. Therefore if there is low ECF Ca2+ there will be little neurotransmitter released. 3) The EPP (Endplate Potential)s ionic mechanism is as follows: when ACh binds to the nicotinic receptor, this is a ligand-gated ion channel but its also a Na+ and K+ channel. There will be a conformation change that will lead to permeability of the motor end plate to Na+ and K+ because of their channels opening. Motor End plate gets depolarized to a point about half way between the Na+ and K+ equilibrium potentials. Its about 0. This depolarization is the EPP. In order to make the EPP you need various MEPPs which are miniature endplate potentials. Every synaptic vesicle produces the smallest possible change in membrane potential of the motor end plate, these are the MEPPs. Each MEPP depolarizes the endplate by 0.4mV. Summing all the MEPPs gives you the EPP. CP03 Multiple Choice Questions 1) Which of the following enzymes catalyzes the synthesis of ACh? E. Choline acetyltransferase 2) GABA usually A. Opens channels permeable to Cl3) Which of the following statements distinguishes excitatory chemical synapses in the brain from the neuromuscular junction? D. Temporal summation and spatial summation onto the postsynaptic cell increase the likelihood that a postsynaptic action potential will be evoked.