NSC 4352 1nd EditionExam # 2 Study Guide Lectures 7-10Lecture 7:Electrotonic spread of potentials vs. “active” spread of the action potential• Electrotonic refers to the "passive" spread of charge inside a neuron."Passive" means that voltage-dependent changes in membrane conductance do not contribute. •Electrotonic spread of the potential describes the attraction of opposite- and reflection of like-charged ions within the cell.•Neurons produce two types of electrical potentials: 1. a non-propagated local potential called an electrotonic potential, due to a local change in ionic conductance (e.g. channel opening due to synaptic response). When it spreads along the membrane, it becomes exponentially smaller. 2. a propagated impulse called an action potential. •Electrotonic potentials from multiple sources (i.e. different synapses) can sum spatially ortem-porally. Because the ionic charge enters in one location and dissipates to others, losing inten-sity as it spreads, electrotonic spread is a graded response. •Electrotonic spread and summation of many inputs is responsible for depolarizing the voltage of the soma sufficiently to threshold and trigger the action potential.•Electrotonic potentials are conducted faster than action potentials, but attenuate rapidly, thusthey are unsuitable for long-distance signaling.•In contrast, the action potential is an all-or-none propagation down the axon of the neuron during which the cur-rent is regenerated.Input Resistance:A. Increases in outward or inward current pulses (A1) produce propor-tional and symmetrical changes in membrane potential (Vm) (A2). Note that the potential changes more slowly than the current steps.B. An I-V curve is obtained by plotting the steady state voltage against the injected current. The slope of the I-V curve defines the input resistance of the neuron.The I-V curve shown here is linear; Vm changes by 10 mV for every 1 nA change in current Passive Membrane Properties – Capacitance:•capacitance (unit = farad) is the ability of a body to hold an electrical charge. •a capacitor is a device that stores energy in the electric field created between a pair of conduc-tors on which equal but opposite electric charges have been placed. •A capacitor consists of two conductors (plates) separated by an insulator (dielectric). •In a parallel plate capacitor, capacitance is directly proportional to the surface area of the con-ductor plates and inversely proportional to the separation distance between the plates.•If the charges on the plates are +Q and −Q, and V gives the voltage between the plates,then the capacitance is given by C= Q/VThe length constant (lambda): The length constant is a measure of the ef-ficiency of the passive spread of volt-age changes along the neuron (“how far?”)Time constant (tau):•The time constant is defined as the time when thevoltage response (Vt) rises to 1 – (1/e) (or 63%) ofthe steady state membrane response (V∞)Lecture 8Properties of single Na+ channels:1. Currents carried by Na+ —> Inward at potentials more negative than ENa and reverse theirpolarity above ENa The amplitude of current depends on Na+ concentration.2. Time course of opening, closing and inactivation matches macroscopic current (C vs. D) —>stochastic events averaged many times.3. Opening and closing of channels are voltage-dependent (E).4. Tetrodotoxin blocks both microscopic and macroscopic Na+ currents.K Channels:•Similarly, properties of single channel K+ currents also reflect macroscopic currents:1. Outward currents2. Do not inactivate during brief depolarizations 3. Are voltage-dependent .- depolarization increases probability of opening; - hyperpolarization closes4. Are blocked by drugs that affect the macroscopiccurrent .—>K+ channel blockers **Nearly 100 K+ channel genes are known; Form distinct groups that differ in their activation, gating and inactivation properties; as well as their pharmacological pro-fileLecture 10:Criteria that define Neurotransmitters1. The substance must be present within the presynaptic neuron.Problems: Transmitters like glutamate, glycine and aspartate have also other functions in cellular metabolism and/or function as precursor for othertransmitters (e.g. dopamine). 2. The substance must be released in response to presynaptic depolarization and the release must be Ca2+-dependent.3. Specific receptors for the substance must exist on the postsynaptic cell.**Release of neuropeptides requires high-frequency stimulation—> Importance of calcium lev-els in the presynaptic terminalThe Neuromuscular junction (NMJ):• Large postsynaptic cell• One axon (but about 100 synapses !)per muscle cell• Highly reliable– Most pre-synaptic action poten-tials lead to a post-synaptic action potential• Chemical signaling is simple– Only one type of ion channelKey variables that characterizequantal(vesicular) release:• the number of release sites (N)• the probability of a quantal release (p)•the size of the quantal response (q)•the distribution of amplitudes of the postsynaptic response can be fitted to a binominal distribution•From this, the best-fitting values of N, p, and q can be extracted —> “quantal analysis”Ca2+ affects the probability of release, not the quantal size:• At the NMJ an action poten-tial normally triggers the re-lease of ~150 quanta, which each generate synaptic poten-tials of 0.5mV.• Normal spontaneous level ofrelease is one quanta per sec-ond. Ca2+ influx increases probability of release 100,000-fold.•At central synapses, an action potential normally triggers the release of only 1-10 quanta.Lecture 10:Synapsin – keeps vesicles tethered in the reserve pool:•cross-links vesicles to cytoskeletal filaments (f-actin)•• regulated by PKA and Ca2+/Calmodulin-dependent kinase (CaMKII)• •Phosphorylation frees vesicles to move.Rab Proteins:•Small GTP-binding protein• Rab GTPases regulate many steps of membrane traffic, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion• more than 60 different Rab proteins are involved in vesicle transportmark transport vesicles •interact with v-SNAREs to initiate fusionCalcium Sensor – Synapto-tagmin-1:• Has two C2 domains (mem-brane-targeting domains)– Binds phospholipids in a calcium-dependent manner– binding of Ca2+ allows it to interact with syntaxin (v-SNARE)• Calcium Sensor– Releases clamp on