Electricity Definitions Voltage (V) – potential energy generated by separated charges Current (I) – flow of charges between points Resistance (R) – hindrance to charge flow Insulator –high electrical resistance Conductor –low electrical resistance

Biological Currents & Resting Potential (Vr) Flow of ions rather than electrons Generated by different [Na+], [ K+], [ Cl], [anionic proteins] and charged phospholipids Ion gradients Differential permeability to Na+ and K+ Sodium-potassium pump 5 mM Ca2+ 1.8 mM 150 mM

Electrochemical Gradient Electrical current created & voltage across the membrane changes when channels open Ions flow down their chemical gradient from high [] to low [] Ions flow down their electrical gradient toward opposite charge Electrochemical gradient The combined potentials of the electrical and chemical gradients taken together [Hi] [Lo] + -

Electrochemical Gradients & Nernst Equation Potential established by equilibrium of ion flow down concentration gradient balanced by repulsion of charges Vr is established when rate of K+ moving out = K+ moving in Nernst equation relates chemical equilibrium to electrical potential EK = [2.3RT/zF](log[Ko]/[Ki]) = 0.061V[log(.005M/.150M)] = -90mV [Hi] - [Lo] + K+

Ion Channels Passive channels Ligand gated channels always slightly open Ligand gated channels opened/closed by a specific ligand Voltage-gated channels opened/closed by change in membrane polarity Mechanically-gated channels opened/closed by physical deformation

Operation of a Ligand Gated Channel

Operation of a Voltage-Gated Na+ Channel

Changes in Membrane Potential Depolarization – the inside of the membrane becomes less negative Repolarization – the membrane returns to its resting membrane potential Hyperpolarization – the inside of the membrane becomes more negative than the resting potential

Graded Potentials Short-lived, local changes in membrane potential Intensity decreases with distance Magnitude varies directly with the strength of stimulus If sufficiently strong enough can initiate action potentials

Action Potentials (APs) A brief reversal of membrane potential with a total amplitude of ~100 mV Only generated by muscle cells & neurons Propagated by voltage-gated channels Don’t decrease in strength over distance

Action Potential: Resting State Na+ & K+ channels closed Some leakage of Na+ & K+ Each Na+ channel has two voltage-regulated gates Activation gates – closed in the resting state Inactivation gates – open in the resting state Figure 11.12.1

Action Potential: Depolarization Phase Na+ permeability increases; Vr reverses Na+ gates opened; K+ gates closed Threshold – critical level of depolarization (-55mV) At threshold, depolarization becomes self-generating

Action Potential: Repolarization Phase Change in polarity closes Na inactivation gates As Na gates close, voltage-sensitive K+ gates open K+ leaves & Vr is restored

Action Potential: Hyperpolarization K gates remain open, allowing excessive efflux of K+ causes hyperpolarization neuron refractory while hyperpolarized

Phases of the Action Potential 1 – resting state 2 – depolarization phase 3 – repolarization phase 4 – hyperpolarization

Action Potential Propagation (T = 0ms) Na+ influx depolarizes patch of axonal membrane Positive ions in axoplasm move toward negative region of the membrane

Action Potential Propagation (Time = 1ms) + Extracellular ions diffuse to the area of greatest - charge Creates current that depolarizes adjacent membrane in forward direction Impulse propagates away from its point of origin refractory refractory

Refractory Periods Absolute - from opening to closing of Na+ activation gates Relative – after closing Na activation gates till K gates are closed

Threshold and Action Potentials ~ 20 mV depolarization Graded potentials subthreshold stimuli that don’t transit to AP threshold stimuli are relayed into AP All-or-none phenomenon – AP either happens completely, or not at all Graded potentials occur along receptive zones of neurons due to presence of only ligand-gated channels AP begins at axon hillock due to presence of voltage-gated channels

Conduction Velocities of Axons Conduction velocities vary widely among neurons Rate of impulse propagation is determined by: Axon diameter – the larger the diameter, the faster the impulse Presence of a myelin sheath – myelination dramatically increases impulse speed

Saltatory Conduction Voltage-gated Na+ channels are located at the nodes of Ranvier Action potentials occur at the nodes and jump from one node to the next because that is only place current can flow through the axonal membrane Much faster than conduction along unmyelinated axons

Synapses Junction for information transfer from one neuron to another neuron or effector cell Presynaptic neuron – conducts impulses toward the synapse Postsynaptic neuron – transmits impulses away from the synapse

Synapses Morphological Types Axodendritic –axon to dendrite Axosomatic –axon to soma Axoaxonic (axon to axon)

Conductance Synapses Types Chemical : release and reception of neurotransmitters presynaptic membrane with synaptic vesicles postsynaptic membrane with receptors Electrical : less common gap junctions important in CNS for: Control of mental arousal Emotions and memory Ion and water homeostasis

Synapse Structure Synaptic cleft Space between pre- and postsynaptic neurons Halts action potential Transmission of signal occurs by neurotransmitter Figure 11.19

Synaptic Events APs reach terminal of presynaptic neuron & open Ca2+ channels Neurotransmitter released into synaptic cleft Neurotransmitter crosses cleft & binds receptors on postsynaptic membrane Postsynaptic membrane permeability changes, causing an excitatory or inhibitory effect

Neurotransmitters >50 identified Classified chemically and functionally Acetylcholine (ACh) Biogenic amines Amino acids Peptides Dissolved gases NO and CO

Neurotransmitters: Acetylcholine 1st neurotransmitter identified Released at neuromuscular junctions Synthesized and enclosed in synaptic vesicles Degraded by enzyme acetylcholinesterase (AChE) Released by: All neurons that stimulate skeletal muscle Some neurons in the autonomic nervous system

Neurotransmitters: Biogenic Amines Broadly distributed in the brain Behaviors and circadian rythyms Catecholamines – dopamine, norepinephrine (NE), and epinephrine Indolamines – serotonin and histamine

Synthesis of Catecholamines Enzymes present in the cell determine length of biosynthetic pathway Norepinephrine and dopamine are synthesized in axonal terminals Epinephrine is released by the adrenal medulla Figure 11.22

Neurotransmitters: Amino Acids Found only in CNS Include: GABA – Gamma ()-aminobutyric acid Glycine Aspartate Glutamate

Neurotransmitters: Peptides Tachykinin & substance P – mediator of pain signals -endorphin, dynorphin, & enkephalins – natural opiates that block pain somatostatin & cholecystokinin – communicate between gut and CNS

Neurotransmitters: Gases Nitric oxide (NO) Activates the intracellular receptor guanylyl cyclase Involved in learning and memory Vascular smooth muscle

Functional Classification of Neurotransmitters Excitatory neurotransmitters cause depolarization (e.g., glutamate) Inhibitory neurotransmitters cause hyperpolarization (e.g., GABA and glycine) Some can be either Determined by receptor on postsynaptic neuron i.e. acetylcholine Excitatory at skeletal neuromuscular junctions Inhibitory in cardiac muscle

Neurotransmitter Receptor Mechanisms Direct: Directly activate (open) ion channels Promote rapid responses Examples: ACh and amino acids Indirect: Bind receptors and act through second messengers Promote long-lasting effects Examples: biogenic amines, peptides, and dissolved gases

Termination of Neurotransmitter Effects Degradation by enzymes (acetylcholinesterase) Absorption by astrocytes or the presynaptic terminals Diffusion from the synaptic cleft

Postsynaptic Potentials Neurotransmitter receptors mediate changes in membrane potential according to: # of receptors activated  the amount of neurotransmitter released The length of time the receptors are stimulated The two types of postsynaptic potentials are: EPSP – excitatory postsynaptic potentials IPSP – inhibitory postsynaptic potentials

Excitatory Postsynaptic Potentials (EPSPs) Graded potentials that initiate action potentials Use only ligand gated channels Na+ and K+ flow in opposite directions at the same time

Inhibitory Synapses and IPSPs Receptor activation increases permeability to K+ and Cl- Makes charge on the inner surface more negative Reduces postsynaptic neuron’s ability to produce an action potential

Summation EPSPs summate to induce an action potential Summation of IPSPs and EPSPs cancel each other out

Neural Integration: Neuronal Pools Functional groups of neurons that: Integrate incoming information Forward the processed information to its appropriate destination

Types of Circuits in Neuronal Pools Divergent – one incoming fiber stimulates ever increasing number of fibers, often amplifying circuits Figure 11.25a, b

Types of Circuits in Neuronal Pools Convergent – resulting in either strong stimulation or inhibition Figure 11.25c, d

Types of Circuits in Neuronal Pools Reverberating – chain of neurons containing collateral synapses with previous neurons in the chain Figure 11.25e

Types of Circuits in Neuronal Pools Parallel after-discharge – incoming neurons stimulate several neurons in parallel arrays Figure 11.25f

Patterns of Neural Processing Serial Processing Input travels along one pathway to a specific destination Works in an all-or-none manner Example: spinal reflexes

Patterns of Neural Processing Parallel Processing Input travels along several pathways Pathways are integrated in different CNS systems One stimulus promotes numerous responses Example: a smell may remind one of the odor and associated experiences