The Membrane Potential Results from: (1) action of Na-K pump (2) permeability of PM (leakage channels) (3) presence of impermeant molecules (fixed anions) yields an observed “charge” at the PM (outside is slightly more positive, inside is slightly more negative) leakage channels + - membrane potential Potential: 2 oppositely charged molecules separated by something. Impt because it is potential energy (stored energy) Orange = sodium purple = potassium. Stars = fixed anions (stable negatively charged; many proteins in cells) Establish membrane potential Na-K pump creates a concentration gradient (pump Na out; K in) (sodium wants to flow inside; potassium is high inside, so wants to flow outside) Use leakage channels: unequal distribution of charges across PM, because there is a tendancy for K to leak more easily than Na. add up charge, is equal. Open channels of the PM Leak allows K to flow out. (K has a positive charge). Occurs at the plasma membrane Fixed anions: draws cations into cell fixed anions Na K

The Membrane Potential of a Cell For a cell: Na-K pump leakage channels fixed anions Around PM, where leakage is occuring, we get + on outside – on inside. Why? Because K (a positive charge) is leaving the cell. Plasma membrane is more permeable to K difference in charge, or potential difference, is the membrane potential; denoted in volts primarily determined by K conc gradient *is only observed at the PM*

Equilibrium Potentials many inorganic ions maintained at specific conc’s within IC & EC contributes to membrane potential, impact of each ion depends on it’s: conc gradient membrane permeability K major role in membrane potential PM more permeable to this ion consider membrane only permeable to K, what would be the membrane potential? K equilibrium potential, EK -90mV (with an internal concen of 150 and external of 5) As the membrane potential is -90, K will not move. Na equilibrium potential, ENa 66 mV (when concentration is 145 outside and 12 mM inside) Na will not move equilibrium Conc gradient and permeability impact how things move across pm Cells control this and use it for communication purpose (impt in excitable cells aka neurons and muscle cells) Answer: Fixed anions want to draw K back in Where K conc is stable, ie no net flow of ion (its at equilibrium). Find membrane potential [K] stable. Trying to find equilibrium potential

example – an excitable cell equilibrium potentials are useful for they explain what happens when the PM becomes more permeable to a particular ion example – an excitable cell permeable to Na, brief pd; membrane potential moves toward ENa at rest -70mV Neuron, apply voltage, and causes a change in permeability to Na. Move toward Ena YET, the membrane potential at rest is close but not the same as the EK

Nernst Equation EX = _______ log ______ diffusion gradients of an ion depend on conc differences equilibrium potential depends on ratio of ion conc on both sides of PM Nernst equation permits calculation of theoretical equilibrium potential for specific ion conc’s known differ between ion species magnitude & direction cation value negative Xi > Xo (internal conc greater than outside) K is (-90) high inside cell Na is (66) high outside cell yet, what happens when more than one ion channel is open? GHK equation (Vm) 61 [Xo] EX = _______ log ______ z [Xi] 61 mM = ____ log __5___ = -90 +1 150 mM = _61_log _____ = +66 mV +1 Allows us to calculate the electrical potential necessary to balance a given ion conc gradient across PM so no net flux of the ion occurs. Adjust permeability of the PM Z = valance of ion.

Goldman-Hodgkin-Katz equation (Vm) Reversed due to Cl is an anion mvt has oppositite effect on membrane PK [Ko] + PNa[Nao] + PCl[Cli] Vm = 61 log PK [Ki] + PNa[Nai] + PCl[Clo] (1)(5) + (0.04)(145) + (0.45)(9) = 61 log = -68 mV (1)(150) + (0.04)(12) + (0.45)(125) Pk Potassium permeability constant Na is least permeable, K is most permeable, Cl is in the middle Cl is an anion (negatively charged), so has different impact on PM Reversed due to Cl is an anion mvt has oppositite effect on membrane K highest permeability, explains wny RMP close to Ek

Resting Membrane Potential (RMP) membrane potential of a cell at “rest”, or a cell in an inactivated state depends on: ratio of conc’s (Xo/Xi) of each ion on both sides of PM specific permeability of membrane to each ion most impt “players” K+, Na+, Ca2+ & Cl- individual contribution dependent on conc differences across PM (can change depending on cell type, tissue or organ) & permeabilities any change in an ions EC conc will change the RMP but only to the extent the membrane is permeable (you can mess with Na conc gradient, but have more impact if you mess with K) change in the cell membranes permeability for any given ion will change its RMP excitable cells cellular range -65 mV to -85 mV

Question Would lowering a neuron’s IC [K] by 1 mM have the same effect on RMP as raising the EC [K] by 1 mM? Confirm with Nernst equation -No; Changing the EC [K] has a greater effect on Ek and thus the RMP. This is because of the ratio of external to internal K is changed more when EC levels go from 5 to 6 mM (20% increase) than IC level lowered from 150 to 149 mM (0.7% increase) No because if

leakage channels always open Role of Na-K pumps RMP is less than the EK suggest that K leaks out & cell not at equilibrium with respect to K conc, or Na conc either ion leakage + EE, results in membrane potential leakage channels always open runs continuously What might be impacting RMP? Not just K leakage, also the electrogenic effect. Na-K pump: you are not moving the same number of positive charge. Electrogenic pump, because it causes an electrogenic effect: unequal transport of charge). Makes outside more positive. RMP is never at K equlibrium potential Na-K pump creates electrogenic effect because it does not pump equal amounts of + and – charge. Helps establish positive on outside; negative on inside If outside is positive and inside is negative. Positive charge will want to flow across (inside) and negative will want to flow outside maintains ion conc’s electrogenic effect unequal transport of + charge (3Na to 2K) by Na-K pump, makes inside “less” positive, or negative MINIMAL on RMP counters leakage

Influences on RMP Fixed negative charge (wants to draw + charge to it) Because of pump make K higher inside Na higher outside Permeability, leakage of K has the MOST effect, electro pump has an effect as well.

Cell Signaling refers to how cells communicate with each other intercellular communication many release regulatory molecules into EC environment general categories paracrine synaptic endocrine Paracrine regulator: regulator molecule released from one cell and effects another cell Synaptic: Directly send messenger from one cell to another Endocrine: Release regulatory molecule to EF, transport through blood or lymphatics, to wherever its target tissue (organ is located) local mechanism functional connection long distance

A = autocrine Autocrine: cell releases reg. molecule that then feeds back on itself. Gap junctions: directly comm. From one cell to another. Flow for fusion of Intracellular space from one cell to another. Can be opened or closed (regulated) GAP JUNCTIONS provide direct communication between cells by fusing PMs and permitting diffusion from one cell’s cytoplasm to the next

target cell must display a R protein for signaling/regulatory molecule Regulatory Molecules LOCATION Target cell: effected by regulatory molecule if it has a signal. More of a change in the extracellular than intracellular to get to the normal Ek Target cell if it has a receptor like cell A. Must have receptor for signaling molecules Neurotransmitters, hormones, paracringe regulators: must decide if they are polar (water soluble) or nonpolar (lipid soluble) Nonpolar (lipid soluble) go right through. Found in the cytoplasm or nucleus. target cell target cell must display a R protein for signaling/regulatory molecule

Signal Transduction Pathways mech for water soluble msgers 2nd messenger systems Regulatory molecules is first messenger, bind to receptor and initiate a second messenger Panel d: g protein. Hormone binds to receptor, activates g protein, alpha subunit then activates effector protein, second messenger then has cellular response Regulatory molecule binds to receptor  activated state  effectors (alpha or beta)  unstimulated state A) open ion channel b) becomes activated enzyme c)binds to receptor, activate enzyme bound to it

Signal Transduction Pathways mech for lipid-soluble msger transcription factor Go across pm, bind to receptor intracellularly. A lot of times found in the nucleus and serves as a transcription factor. Message then goes out; transcribe, translate and end up with synthesis of a protein that is then going to cause cellular response

Cessation of Activity in Signal Transduction impt b/c chronic overstimulation can be detrimental to cell detrimental to the cell key event is stopping R activation (1) decrease conc of 1st msger (2) R becomes chemically altered, lowers affinity for 1st msger (3) R becomes phosphorylated, prevents G-protein binding (4) R-ligand complex endocytosed, removed R from PM Happens for as long as reg molecule is bound to the receptor Decrease conc of 1st messenger (quit making reg molecule and you will have stopping of simple transduction pathway 2) seen in water soluble category 4) if we don’t have receptor on pm, target cell will not respond to reg. molecule. Mechanisms utilized to stop signal transduction pathways.