Membranes, Transport, and Potentials

• Week 2 lecture content covers membranes, transport, and potentials.
• The primary topics are peripheral nervous systems and muscle contraction.
• A review of cell biology knowledge about crossbridge formation is recommended.

Learning Outcomes

• Intracellular impermeable anions and the Na+/K+ pump maintain asymmetric ion distribution across cell membranes.
• Diffusion and semipermeable membranes explain consequences regarding Na+ and K+ distribution.
• Ion movement during action potentials is facilitated by voltage-gated and ligand-gated channels, is crucial for initiating action potentials.
• Membrane transport for Sodium (Na+) and membrane potentials for Potassium (K+) are vital for action potential generation.
• Action potentials have a relationship with threshold and frequency coding.
• Myelination affects neuronal communication through the saltatory conduction process.

Cell and Ion Gradients

• Gradients are due to the laws of physical chemistry, with energy input required to maintain them.
• Intracellular ion concentrations:
• K+: 142 mM
• A-: 132 mequiv/L
• Cl-: 10 mM
• Na+: 10 mM
• Ca2+: 0.1 μM
• Mg2+: 1.0 mM
• HCO3-: 10 mM
• pH: 7.0
• Extracellular ion concentrations:
• K+: 4 mM
• A-: 10 mequiv/L
• Cl-: 118 mM
• Na+: 143 mM
• Ca2+: 1.5 mM
• Mg2+: 1.0 mM
• HCO3-: 24 mM
• pH: 7.4
• A- represents fixed negative charges on macromolecules.

Ion Gradient Principles

• Cells accumulate proteins, which generally have a negative charge and can't cross the membrane.
• Cell membranes without energy input are semi-permeable to common ions.
• Permeability details: Permeable to K+ and impermeable to Na+
• Potassium (K+) accumulates where impermeable anions (A-) are located, which results in high intracellular K+ concentration.
• Sodium (Na+) leaks into cell and is pumped out against its concentration gradient by a Na+/K+ pump, requiring ATP hydrolysis (primary active transport).

Potassium in Membrane Potentials

• Intracellular Potassium [K+] is greater than extracellular [K+].
• K+ tends to diffuse out of the cell.
• K+ loss leads to a small residual negative charge on inner side of the membrane, establishing an electrochemical equilibrium.
• An increased extracellular [K+] reduces the diffusion tendency, requiring a less negative membrane potential.
• An increased extracellular [K+] depolarizes the membrane.
• The Nernst equation determines the exact relationship between membrane potential (Em) and extracellular [K+].

Resting Membrane Potential

• All cells have a resting membrane potential.
• Resting membrane potential: This charge difference across the cell membrane where the cytoplasm side is negative relative to the extracellular fluid.
• Resting membrane potential ranges from −20 to −95 mV, varying by cell type.

Ion Channels

• Ions move across cell membranes via ion channels, which:
• Are protein pores spanning the phospholipid bilayer.
• Classified by their gating stimulus.
• Types of ion channels:
• Voltage-gated: Activated by changes in membrane potential.
• Ligand-gated: Activated by extracellular chemicals binding to a receptor that is an ion channel.
• Voltage-gated channels:
• Support action potentials, especially in nerve and muscle cells.
• Named for their primary permeable ion: Na+, K+, Ca2+.
• Includes families of channels for specific ionic species.
• Ligand-gated channels:
• Open when a ligand binds to them.
• Found in muscle, nerve, and secretory cells.
• Can be cation-selective (Na+ influx, causing depolarization and increased excitability) or anion-selective (Cl- influx, causing hyperpolarization and decreased excitability).
• Example: Nicotinic acetylcholine receptor at the nerve-skeletal muscle junction.

Action Potentials

• Action potentials: A transient depolarization of a cell.
• Excitable cells: Cells that generate action potentials.
• An action potential: Of fixed magnitude and duration for a particular cell.
• Information transfer involves coding via action potential frequency along a nerve via sensory cells to the central nervous system, and cellular events triggered includes muscular contraction.
• All-or-nothing principle: Once an action potential is initiated, stimulus strength won't alter its configuration.
• The cell membrane must depolarize to a critical (threshold) potential for it to initiate.
• Action potential "upstroke" (depolarization) results from a temporary increase in membrane Na+ permeability and it was confirmed by experimentation.
• Action potential termination: The membrane potential repolarizes to its resting state and then repolarization is aided by increased K+ permeability.

Action Potential Process

• Begin at the resting membrane potential.
• Threshold: voltage-gated Na+ and K+ channels begin to open in response to a depolarizing stimulus.
• Rapid Na+ entry depolarizes the cell.
• Peak: Na+ channels close, and slower K+ channels open.
• K+ moves from inside the cell to the extracellular fluid.
• K+ channels remain open and additional K+ leaves the cell which hyperpolarizes the cell.
• Voltage-gated K+ channels close, and the less K+ leak brings membrane potential back to resting levels.

Initiating an Action Potential

• A cell must be depolarized from resting membrane potential (Vm) to a threshold potential (Vth) to begin an action potential (AP).
• Voltage-activated ion channels open and let cations (usually Na+) into the cell at threshold, thus generating the action potential.
• Stimulus needed: To initiate action potential, which results from the magnitude of the stimulus determining excitability.
• High excitability: Only a small stimulus needed.
• Low excitability: A larger stimulus needed.
• Going from resting to threshold potential:
• It can be achieved artificially by the use of electrical current application.
• Via the binding of neurotransmitters to ligand-gated channels at synapses/junctions on the target cell.
• It can be reached by using spontaneously in "pacemaker" cells in the heart pacemaker.
• Resulting from the conversion of stimulus to changes in membrane potential in associated nerves in sensory cells.

Action Potential Conduction

• The local circuit hypothesis: The local and electrical current leads the potential action
• Trigger Zone: This region generates the Action Potential, and represents the reversal of membrane potential
• Depolarisation that has occurred as well as its sufficiency helps in reaching an action potential initiation

Factors Affecting the AP Conduction Velocity (CV)

• Cell diameter: CV increases with fibre diameter.
• Temperature: CV generally increases with temperature.
• Myelinated fibres:
  • They are fibres >1μm in diameter with myelin sheath, that has breaks, and surrounds every millimetre.
  • Myelin greatly increases because there are AP jumps from node to node, known as saltatory conduction.

Coding Information

• Stimulus strength increases as the number of action potentials increases.
• Action potential frequency codes stimulus intensity, carrying information of the nervous system via a nerve.

Consequences of Low Intracellular Na+

• The cell expends a lot of energy to maintain low intracellular [Na+]. To exploit energy:
• Glucose transport into the cell.
• Na can move into a specific transporter and drag glucose with it.
• Energy eventually is used when Na is pumped from the cell.
• Protein GLUT in this instance, is an important secondary active transporter
• Kidney: retrieval of glucose from the small
• Gut: uptake of glucose from the small