BIOB34 Module 7 Part 1

Page 1:

• Definitions of current (I) and electrical synapse

  • Current is the flow of charge, such as movement of electrons or other ions

  • Electrical synapse refers to gap junctions in cardiomyocytes

Page 2:

• Definitions of voltage (V) and resistance (R)

  • Voltage describes the electrical driving force or potential difference between two points

  • Resistance is the opposition to the passage of current

  • Ohm's Law states that current (I) is equal to voltage (V) divided by resistance (R)

Page 3:

• Difference between AC and DC currents

  • AA batteries provide DC voltage of approximately 1.5 V

  • Electrical outlets in North America provide AC voltage of 115/120 V with a frequency of 60 Hz

  • In an electric circuit, electrons flow from the negative terminal to the positive terminal, but the positive current moves in the opposite direction

Page 4:

• DC currents in biological phenomena

  • Some biological phenomena, like blood pressure, behave like DC currents (flow of fluid, not charge)

  • DC currents flow in one direction only and do not cross 0 V

Page 5:

• AC currents in biological signals

  • Some biological signals, like action potentials, are AC currents

  • There can be a net positive current into or out of a cell

Page 6:

• Hertz (Hz) as a unit of frequency

  • Hertz measures the number of complete cycles per second

  • North American electricity has a frequency of 60 Hz, meaning it passes 0 V 120 times per second

Page 7:

• Fluorescent lighting and AC power

  • Any strong voltage causes a fluorescent tube to emit light, regardless of polarity

  • Fluorescent lighting dims when the voltage equals 0, which happens 120 times per second with 60 Hz AC power

Page 8:

• Flow of ions and ionic current

  • Ions have both physical mass/volume and charge

  • Their movement and distribution are influenced by both chemical and electrical forces

  • Gradients in concentration and charge can be in the same or opposite directions

Page 9:

• Equilibrium potentials for K+ and Cl-

  • Initially, there is no electrical gradient, but there is a concentration gradient

  • More K+ and Cl- ions are present in one side compared to the other

Page 10:

• Movement of K+ down its concentration gradient

  • When the membrane becomes permeable to K+ only, K+ moves down its concentration gradient

  • At this point, no charge gradient has been built up

Page 11:

• Development of net charge difference

  • As K+ moves, a net charge difference develops, making one side more positive than the other

  • The driving force of the electrical gradient becomes equal to the driving force of the concentration gradient

  • The total movement of K+ is minimal, and the membrane acts as a capacitor

Page 12:

• Convention of outside of the cell being 0

  • By convention, the outside of the cell is considered to have a potential of 0

  • Membrane potential readings are relative to the outside

Page 13:

• Movement of Na+ down its concentration gradient

  • When the membrane becomes permeable to Na+ only, Na+ moves down its concentration gradient

  • At equilibrium, the membrane potential reading is +58 mV

Page 14:

• Work required to move chemical species and charged particles

  • The work required to move a chemical species is determined by the natural logarithm of the concentration ratio

  • The work required to move a charged particle across an electrical gradient is determined by the product of the number of charges per particle, Faraday's constant, and the potential gradient

Page 15:

• Application of the Nernst equation

  • The Nernst equation calculates the equilibrium potential for a specific ion

  • The equilibrium potential for K+ is -58 mV, as predicted by the equation

  • At equilibrium, there is no net flux because the electrical work cancels out the chemical work

Page 16:

• Frog Muscle Cell Resting membrane potential (Vm) measured Vm = -92 mV

• [A-] = proteins, DNA, RNA, macromolecules (essentially fixed inside the cell)

• [Ca2+] = free intracellular Ca2+ only

Page 17:

• Membrane potential can be experimentally or estimated using the Goldman equation

• Concentrations and relative permeabilities of ions are involved in establishing the membrane potential

• Na+, K+, and Cl- are the biggest players in establishing the membrane potential

• In frog muscle: PK is 100 times greater than PNa, PCl is extremely small (membrane almost impermeable to Cl-)

Page 18:

• Na+ and K+ are the most important players when the membrane is at rest

• The membrane potential (Vm) of a frog muscle cell is -92 mV

Page 19:

• Examples of ion channels found in axons and their characteristics

• Leak channel (open IK (leak)) produces relatively high PK of resting cell

• Voltage-gated Na+ channel produces the rising phase of depolarization

• Voltage-gated Ca2+ channel produces slow depolarization and allows Ca2+ to enter the cell

• Voltage-gated K+ channel carries current that rapidly repolarizes the membrane

• Ca2+-dependent K+ channel carries current that repolarizes the cell following elevated cytoplasmic [Ca2+]

Page 20:

• When a positive stimulus current is applied to an excitable cell, the membrane potential changes

Page 21:

• Hyperpolarization (inward current) causes the membrane potential to become more negative

• Depolarization (inward current) causes the membrane potential to become closer to 0

Page 22:

• If threshold isn't reached, no action potential (AP) will fire

• All-or-none phenomenon: once threshold is reached, the intensity of the stimulus is no longer directly related to the intensity of the AP

• Local response occurs when the stimulus is just shy of the threshold

Page 23:

• Compound Action Potential is the sum of individual APs

• Stronger stimulus leads to more axons firing and a larger compound AP

• Minimum stimulus intensity is the intensity necessary to trigger at least one or a few axons to fire an AP

Page 24:

• The Hodgkin Cycle is one of the few positive feedback cycles that occur in biological systems

Page 25:

• Action potentials (APs) are the result of voltage-gated ion channel activity

• Na+/K+ ATPase pump is not directly responsible for repolarization after an individual AP

Page 26:

• Equilibrium Potential is the membrane potential at which there is no net movement of a specific ion across the membrane

• Thinking about the electrochemical gradient for Na

Page 27:

• Thinking about the electrochemical gradient for K

Page 28:

• Na+/K+ pump does NOT directly cause repolarization

  • Na+/K+ ATPase pump helps to maintain ion concentrations

  • Contributes to Vm being negative

  • Activated by increased [Na+]in and [K+]out due to action potentials (APs)

  • Takes many APs before pump activity increase is noticeable

Page 29:

• Refractory period

  • Absolute: AP cannot be triggered regardless of stimulus intensity

  • Relative: Excitability is reduced, threshold is higher, resulting AP is weaker

Page 30:

• Depolarization from stimulus affects AP threshold

  • Slow depolarization leads to higher threshold or no AP

  • Synchronization of opening of voltage-gated ion channels is important for understanding refractory periods and stimulation thresholds

Page 31:

• Rapid closing of voltage-gated Na+ channel makes individual channel refractory

Page 32:

• Variation in opening/inactivation timing among population of voltage-gated ion channels

• Absolute refractory period: Too many inactivated Na+ channels for successful AP

• Relative refractory period: Only some Na+ channels ready, higher threshold, less intense AP

Page 33:

• Crab merus nerve: The Refractory Period

• Stimulating electrodes

• Recording electrodes

Page 34:

• Compound Action Potentials

• Absolute refractory period: Membranes of all axons at stim. electrodes are refractory, no compound AP

• Relative refractory period: Membranes of some axons at/near stim. electrodes are refractory, smaller compound AP

Page 35:

• Ion channel refractory behavior makes AP propagation unidirectional from site of initiation

Page 36:

• Current movement along an axon: length constant

• Detection of Vm disturbance decreases exponentially away from site of stimulus

Page 37:

• Length constant (λ): Distance over which Vm decays by 63%

• To increase conduction velocity:

  • Decrease magnitude of denominator (r)

  • Increase numerator (rm - insulate segments of axon with myelin sheaths)

Page 38:

• Invertebrate solution for faster AP conduction: larger axons

• Earthworm nerve cord has many axons, 5 giant axons conduct APs the fastest

Page 39:

• Invertebrate solution for faster AP conduction: larger axons

• Squid can grow quite large, rapid conduction of AP along motoneuron axon is required for jet propulsion

Page 40:

• Increased rm: myelination

• Oligodendrocyte (CNS only)

• Schwann cell (PNS only)

Page 41:

• Myelin sheaths increase membrane resistance (rm) to charge flow

• Reduce membrane capacitance, charge flows better along axon

• APs can only occur at Nodes of Ranvier where myelin is not present

Page 42:

• Saltatory conduction

• APs "jump" or "leap" from node to node

• Elevation of intracellular [Na+] depolarizes the membrane at the next node, causing voltage-gated Na+ channels to open there

Page 43:

• Saltatory conduction

• Action potentials propagate from node to node

• Direction of propagation is towards synaptic terminals

Page 44:

• Understanding cell-to-cell communication in excitable cells involves understanding synaptic function

• APs, graded potentials, synapse, and membrane function contribute to circuit complexity

Page 45:

• Electrical synapses

• Assemblages of gap junctions

• Allow flow of ions, H20, and small molecules

• Fastest type of synapse

• Found in neurons of 'escape behavior' circuitry, common in simplest nervous systems

Page 46:

• Electrical synapse function

• Injection of small stimulus current into cell A leads to graded depolarization in cell B

• Signal in cell B looks like the one in cell A

Page 47:

• Graded potentials travel short distances

• Magnitude of graded potential decreases with increasing distance from opened ion channel

• Decrement due to leakage of charged ions, electrical resistance of cytoplasm, and electrical properties of membrane

Page 48:

• Electrical synapse function

• Suprathreshold stimulating current injected into cell A leads to AP firing in cell A

• Depolarization of cell B beyond threshold elicits AP in cell B

Page 49: Rectifying electrical synapse

• Asymmetric electrical synapses exist

• Opening of gap junctions is elicited by depolarization

• Connexon channels on only one of the two membranes may respond strongly to depolarization and open

• This can make some electrical synapses one-way-only (rectifying)

Page 50: Fast chemical synapse

• Ligand-gated ion channels

• Small cleft

• Vesicles released at specialized active zone

Page 51:

• Degraded by enzymatic catalysis

• Diffuses out of cleft

• Re-synthesized for later release

• Transmitter rapidly removed from cleft

• Some removed transmitter recycled into synaptic vesicles

• Fast chemical synapses involve ligand-gated ion channels

• Binding of ligand (neurotransmitter) causes ion channel to open

• Nature of post-synaptic membrane response dictated by channel properties

Page 52: Neurotransmitters and fast chemical synapses

• Table 6-2: Typical small neurotransmitters, their structures, and functions

• Acetylcholine (ACh): Fast excitation; slow inhibition

• y-Aminobutyric acid (GABA): Fast inhibition; slow inhibition

• Effect of a neurotransmitter depends on the properties of the postsynaptic cell

Page 53: Nicotinic synapse

• Presence of ligand-gated ion channel on post-synaptic membrane

• Ligand = Acetylcholine (ACh)

• Nicotine mimics action of ACh

• ACh binding results in depolarization of post-synaptic membrane

Page 54: Nicotinic synapse

• Patch-clamping of individual nicotinic acetylcholine (ACh) receptor channels

• Vm held at ≈ -120 mV (voltage clamping)

• Intermittent binding of agonist (e.g. nicotine) causes channels to flicker open/closed

• Inward positive current transiently measured

Page 55: Nicotinic synapse

• Channel can flicker open/closed while ACh is bound

• "Desensitized" state

• ACh is broken down by acetylcholinesterase in cleft

• Recycled in axonal terminal

• Channel is a "non-selective cation channel": permeable to both Na+ and K+, and sometimes also Ca2+

Page 56: Electromotive force: EMF

• The electromotive force (EMF) is the driving force for movement of an ion

• It is the sum of the strength of electrical and chemical gradients

• EMF can be represented as the difference between Vm and the equilibrium potential for an ion

Page 57: Ionic conductance

• The ionic current for ion X is the magnitude of its driving force multiplied by its permeability

• Ionic current can be represented as the product of conductance and the difference between Vm and the equilibrium potential for ion X

Page 58: Ionic conductance

• This equation is a variation of Ohm's Law

• Ionic current (Ix) = Voltage (Vm) / Resistance (Rx)

• So, Ix = gx * (Vm - X)

Page 59: Reversal Potential

• When current (Ix) for one ion is equal and opposite to another, there is no net current

• The reversal potential can be calculated using the equation: I = (r * gK) + (r * gNa)

Page 60: Reversal Potential

• Different scenarios based on the relationship between INa and IK

• Depending on the net current, there can be depolarization or hyperpolarization when ACh binds

Page 61: GABA fast inhibitory synapse

• Normally, ECl ≈ -100 mV, similar to EK

• When GABA activates channel permeable to Cl-, there is a net Cl- entry and hyperpolarization

Page 62: Slow chemical synapse

• Neurotransmitters are typically larger molecules compared to fast synapses

• Larger vesicles are not released at specialized "active site"

• Indirect action

Page 63:

Slow chemical synapse (typical mechanism)

• Mechanism of neurotransmitter release from axon is essentially equivalent to fast chemical synapse

1. Neurotransmitter binds to receptor

2. This causes activation of associated G-protein complex

   • G-protein complex directly or indirectly causes change in conductance through ion channel

   • Opens or closes channel depending on synapse

3. G-protein activated second messenger systems can cause other cell changes act longer term

Page 64:

Neurotransmitter recycling

• Neurotransmitter deactivated or removed from synapse

• Transmitter (or breakdown products) endocytosed

• In fast chemical synapses, transmitter typically produced & reformed/repackaged in axon terminus

• In slow chemical synapses, transmitter typically produced & reformed/repackaged in soma

• Involving intracellular trafficking

Page 65:

Four functional neural zones

• Signal reception

  • Dendrites and the cell body (soma)

  • Incoming signal received and converted to change in membrane potential

• Signal integration

  • e.g. axon hillock

  • Strong signal is converted to an action potential (AP)

• Signal conduction

  • Axon (some wrapped in myelin sheaths)

  • AP travels down axon

• Signal transmission

  • Axon terminals

  • Release of neurotransmitter/e