Cell Physiology

Cell Physiology Cell Membranes, Transport Across Cell Membranes, Osmosis, Membrane Potentials Lectured by Bien Nillos, MD

The Cell Membrane

Lipid Bilayer 

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Phospholipids – hydrophilic heads and two fatty acid tails (hydrophobic). Hydrophobic tails face each other and form a bilayer. Lipid-soluble substances – cross cell membranes Water-soluble substances – cannot dissolve in the lipid membrane.

Proteins 

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Integral Proteins – span the entire membrane, include ion channels and transport proteins. Peripheral Proteins – located on either the intracellular or extracellular side of the cell, include hormone receptors.

Intercellular Connections 

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Tight junctions – zonula occludens, attachments between cells; may be an intercellular pathway for solutes (impermeable vs. permeable) Gap Junctions – attachments between cells that permit intercellular communication.

Transport Across Membranes 

DOES NOT REQUIRE ENERGY

• Simple Diffusion – “downhill” Permeability – the ease with which a solute diffuses through a membrane  Factors that increase permeability – inc. oil/water partition coefficient, dec. radius of the solute, dec. membrane thickness 

Let’s Imagine This…..

Let’s Imagine This…..

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DOES NOT REQUIRE ENERGY: • Facilitated Diffusion: “Downhill” More rapid than simple diffusion  Exhibits: • Stereospecificity • Saturation • Competition 

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REQUIRES ENERGY: • Primary Active Transport: “Uphill”  Requires direct input of metabolic energy in the form of ATP  Is carrier-mediated.  Examples: Na-K-ATPase Pump, CaATPase pump, H-K-ATPase pump (proton pump).

Let’s Imagine This…..

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REQUIRES ENERGY: • Secondary Active Transport: “Uphill”  Transport of two or more solutes is coupled • One of the solute (usually Na) is transported downhill and provides energy for the “uphill” transport of the other solute.

Osmosis 

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Osmolarity – concentration of osmotically active particles in a solution Can be calculated using the following equation: • Osmolarity = g x C • Where g – number of particles in a solution • C – concentration (mol/L)

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Osmosis – the flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration.

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Osmotic pressure increases when the solute concentration increases.

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Isotonic – two solutions having the same effective osmotic pressure Hypertonic – the solution with higher effective osmotic pressure Hypotonic – the solution with the lower effective osmotic pressure

* Water flows from the hypotonic to the hypertonic solution

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Reflection coefficient – describes the ease with which a solute permeates a membrane (value = 0 to 1) • if 1 = solute is impermeable, creates an osmotic pressure, causes water flow. • If 0 = solute is completely permeable, will not exert any osmotic effect.

Diffusion Potential, Resting Membrane Potential and Action Potential 

Ion channels – integral proteins that span the membrane and when open, permit the passage of certain ions. • Are selective • May be open or closed • Conductance depends on the probability that the channel is open; the higher the probability that a channel is open, the higher the conductance or permeability.

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Voltage-gated channels – are opened or closed by changes in membrane potential Ligand-gated channels – opened or closed by hormones, second messengers or neurotransmitters.

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Diffusion potential – potential difference generated across a membrane because of a concentration difference of an ion. • Diffusion potential can be generated only if the membrane is permeable to the ion. • The size of the diffusion potential depends on the size of the concentration gradient.

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The equilibrium potential is the diffusion potential that exactly balances the tendency for diffusion caused by a concentration difference. At electrochemical equilibrium, the chemical and electrical driving forces that act on an ion are equal and opposite, and no more diffusion of the ion occurs.

Approximate values for Equilibrium potentials in Nerve and Muscle 

ENa = +65 mV

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ECa2 = +120 mV

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EK = -85 mV

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ECl = -85 mV

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Resting membrane potential – expressed as the measured potential difference across the cell membrane in millivolts. By convention, it is expressed as the intracellular potential relative to the extracellular potential.

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Each permeable ion attempts to drive the membrane potential toward its equilibrium potential. For example: the resting membrane potential of nerve is -70 mV which is close to the calculated K+ equilibrium of -85 mV, but far from the calculated Na+ equilibrium potential (+65 mV); thus, at rest, the nerve membrane is far more permeable to K than Na.

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Depolarization – makes the membrane potential less negative (the cell interior becomes less negative) Hyperpolarization – makes the membrane potential more negative Inward current – the flow of positive charge into the cell. Outward current – flow of the positive charge out of the cell.

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Action potential – property of excitable cells that consists of a rapid depolarization or upstroke, followed by repolarization of the membrane potential. Action potentials have stereotypical size and shape, are propagating and are all-or-none.

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Threshold – the membrane potential at which the action potential is inevitable. Inward current depolarizes the membrane. If the inward current depolarizes the membrane to threshold, it produces an action potential.

Resting membrane potential – is approx. -70 mV, cell negative; the result of the high resting conductance to K+ which drives the membrane potential toward the K+ equilibrium potential. Note: at rest, the Na+ channels are closed and Na+ conductance is low. 

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Upstroke – inward current depolarizes the membrane potential to threshold. Depolarization causes rapid opening of the activation gates of the Na+ channel, and the Na+ conductance of the membrane promptly increases.

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Depolarization also closes the inactivation gates of the Na+ channel. Depolarization slowly opens K+ channels and increases K+ conductance to even higher levels than at rest. Repolarization is caused by an outward K+ current.

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Absolute Refractory Period – period during which another action potential cannot be elicited no matter how large the stimulus. Relatively refractory period – an action potential can be elicted during this period only if a larger than usual inward current is provided.

Absolute Refractory Period

Relative Refractory Period

Resting Membrane Potential

-70 mV -85 mV

Time in seconds

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Accommodation – occurs when the cell membrane is held at a depolarized level such that the threshold potential is passed without firing an action potential (e.g. hyperkalemia in skeletal muscles)

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Propagation of Action Potentials – occurs by the spread of local currents to adjacent areas of membrane which are then depolarized to threshold and generate action potentials.

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Conduction velocity is increased by: • Increase in fiber size – increasing the diameter of a nerve fiber results in decreased internal resistance. • Myelination – myelin acts as an insulator around nerve axons and increases conduction velocity (saltatory conduction)

BREAK

QUIZ A

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SOLUTION 1

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SOLUTION 2