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### 54 Cards in this Set

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 CURRENT net flow of charges measured in amperes (A) POTENTIAL DIFFERENCE (E) the WORK needed to move a unit of test charge in a frictionless matter from one point to another measured in volts (V) to move 1 coulomb of charge ax a 1 volt difference requires 1 Joule of work (potential = voltage = voltage difference) ELECTRICAL CONDUCTANCE (G) conductance is defined by OHM'S LAW measures the ease of flow of current between two points where I = GE I (current) = G (conductance) E (voltage difference) measured in units of siemens (S) OHM'S LAW V = IR or I = GV (aka I=gE) voltage = current x resistance current = conductance x potential difference Vrest RESTING MEMBRANE POTENTIAL the voltage drop (Vm) across a membrane due to a separation of charge across the membrane (capacitor) in the absence of any other stimulus or input the membrane functions as what in terms of charge separation? A CAPACITOR components of plasma membrane a. lipid bilayer (phospholipids, cholesterol, glycolipids) b. ion channels (allow ions to flow down electrochemical gradient) c. active transporters/pumps: move ions against their concentration gradients role of plasma membrane in Vrest 1. separates charged substances 2. Imparts capacitance 3. Provides the stuctural framework for subcellular localization (lipid rafts) 4. Is a substrate for enzymes of specific signaling cascades Typeical Vrest: -40 to -90 mV (=10^-3 V) DEPOLARIZATION reduction in charge separation (i.e. making it less negative; e.g. -70 mV to -30 mV) HYPERPOLARIZATION an increase in charge separation (e.g. -70 mV to -100 mV) FREE IONIC CONCENTRATION for a vertebrate SPINAL CORD NEURON Na+ [Na+]out/[Na+]in ratio out:in = Eion = [117]out/ [30]in Ratio out:in = 4 Eion= +36mV FREE IONIC CONCENTRATION for a vertebrate SPINAL CORD NEURON K+ [K+]out/[K+]in ratio out:in = Eion = [3]out/ [90]in Ratio out:in = 0.033 Eion= -90 mV FREE IONIC CONCENTRATION for a vertebrate SPINAL CORD NEURON Cl- [Cl-]out/[Cl-]in ratio out:in = Eion = [120]out/[4]in Ratio out: in = 30 Eion = -90mV FREE IONIC CONCENTRATION for a vertebrate SPINAL CORD NEURON: Anions- [anions-]out/[anions-]in [0]out/[116]in NERNST EQUATION used to find membrane potential with respect to ion concentrations inside and outside the cell E (k+) = constant x log [K+] out/ [K+]in PRINCIPLE OF MACROSCOPIC ELECTRICAL NEUTRALITY equal number of positive and negative charges given the principle of macroscopic electrical neutrality, how then does membrane potential arise from a separation of charges? 1. membrane is SELECTIVELY PERMEABLE (at rest it will allow some ions to cross more readily than others) 2. There is an UNEVEN DISTRIBUTION OF INDIVIDUAL ION SPECIES on the inside versus the outside of the cell what provides the pathway for ions that mediate rapid signalling to move across the membrane? ION CHANNELS what paintains the concentration gradients? ION PUMPS (TRANSPORTERS) ION CHANNELS integral membrane proteins: hetero-oligomeric complexes a) high probability of being opened at Vrest (non-gated or leak channels) b) opened only by specific stimulus (gated) -voltage-gated -ligand gated -mechanosensory (pacinian corpuscles) characteristics of ion channel function SELECTIVE PERMEABILITY (let only specific ions through) CONDUCTANCE: ~10^8 ions/second (much greater than conductace of pumps/transporter) MEAN OPEN TIME: 0.1-100 msec PASSIVE FLUX: no energy required main differences between functions of ion channels and pumps channels- greater conductance, passive flux, open longer Patch clamp technique allows measurement of current flow through a single ion channel or an ensemble of active ion channels (e.g. synaptic currents or whole cell currents) Vrest arises because: 1. there are unequal concentrations (and therefore unequal driving forces) for ions inside and outside the cell 2. because certain ion channels (mainly K+ channels) have a higher probability of being open at rest for a neuron at Vrest, membrane has many channels open for what type of ion? K+ very few types of other channels are open for a neuron at Vrest what forces influence K+ movement CONCENTRATION GRADIENT (pushes K+ ions out of cell) ELECTRICAL GRADIENT (pushes K+ ions into the cell) Ek EQUILIBRIUM POTENTIAL definied point at which the concentration gradietn pushing K+ out will be exactly equal to the electrical gradient holding them in Equilibrium Potential is predicted by what? NERNST EQUATION Eion = 58log [ION]out/[ION]in At equilibrium potential for any given ion (Eion) describe current NO NET CURRENT FLOW FOR THAT ION Ek (Equilibrium potential for K+) in a typical neuron Eion= -90mV What percentage of intracellular K+ ions must leave cell to generate Vrest? <<<<1% (10^-12 moles) charge separation is limited to what area? limited to the area at the faces of the bilayer? electrical neutrality is conserved in terms of: concentrations of ions in bulk solution RESTING MEMBRANE POTENTIAL IS PRIMARILY (but not completely) DETERMINED by: Ek Contribution of Chloride ions to Vrest in most nerve cells conductance for chloride (Gcl) is very small, and Cl- ions are passively distribtued according to Vrest est. by Ek Vrest of muscle cells SIGNIFICANTYL DEPENDS UPON RESTING Cl- conductance Contribution of sodium ions to Vrest permeability of Na+ (at rest) is small compared to permeability to K+ at rest Pna: Pk = ~0.03 MEMBRANE POTENTIAL (Vm) will be determined by: a weighted average of the NERNST POTENTIALS for each permanant ion and their conductances (Gion: think # of open channels) of these ions For most neurons at rest, consider these ions in determining Vm K+ and Na+ Why does Vrest end up being so much closer to Ek than to Ena? because conductance of sodium is so much less than conductance of potassium ions Gna << Gk At Vrest Itot (current flow) = Itot = 0 by definition this system is at rest, there is NO NET CURRENT FLOW At Vrest which ions are at their individual equilibrium potential? NONE OF THE INDIVIDUAL IONS IS AT ITS EQUILIBRIUM POTENTIAL current flows through each class of channels; magnitude of this current is determined by the: 1) CONDUCTANCE (similar to permeability, i.e. # of open channels, and rate of flux through each) 2) DRIVING FORCE equation (how much the Vrest differs from the Eion) At Vrest current of Na+ current of K+ constant inward current of Na+ ions constant outward current of K_ ions however, net current = 0 what structures are required to maintain ionic gradients? PUMPS OR MEMBRANE TRANSPORT PROTEINS ATPases (Na+/K+) ION EXCHANGE PUMPS (Na+/Ca++ and Na+/H+ exchangers) Na+/K+ pump 1. integral membrane protein 2. active transporter (requires ATP) 3. maintains long-term membrane potential 4. controls cell volume and drives active transport of sugars and aas 5. 20-40% of brain's energy use is to power this pump 6. in electically active nerve cells, it is 70% of cell's energy requirement 7. digitalis glycosides (e.g. ouabain) inhibit the pump from the outside by competing with K+ for its binding site 8. for every molecle of ATP hydrolysed, 3 Na+ are pumped out and 2 K+ are pumped in (pump is ELECTROGENIC- will slightly hyperpolarize Vrest from predicted value) 9. pump is NOT needed to generate individual action potentials (these occur by passive flux of ions running down their electrochemical gradients) 10. sometimes pump activity will alter electircal signalling (eg in small axons, high frequency stimulation will lead to a prolonged hyperpolarization as the pump extrudes Na+) disease associated with abdnormal resting potential MYOTONIA CONGENITA (fainting goats?) What does it mean, that the Na/K+ pump is ELECTROGENIC? that it will slightly hyperpolarize Vrest from what is predicted based solely on ion channel activities what generates individual action potentials or graded potentials (receptor potentials, synaptic potentials) PASSIVE FLUX of IONS running down their electrochemical gradients Energy requirements of Na/K+ ATPase 20-40% of brain's energy is used to power this pump in electrically active cells, it is 70% of cell's energy requirement ouabain inhibits what? the Na/K+ ATPase, by competing with K+ for its binding site on the outside of cell In skeletal muscle Vrest is primarily dependent upon: Gcl (conductance of Chloride ions) (Gcl >> Gk) what kind of mutation gives rise to myotonia congenita? mutation in CLCN1 gene (encodes subunit of the predominant Cl channel expressed in skeletal muscle) what happens in myotonia congenita? temporary stiffness induced by forceful, abrupt movement muscle is characterized by an abnormally low resting Gcl: does not allow rapid repolarization following an action potential and relaxation of contraction in the muscle following an initial contraction/movement what characterizes muscle in myotonia congenita? an abnormally low resting Gcl does not allow rapid repolarization following an action potential and relaxation of contraction in the muscle following an initial contraction/movement.