††††††††††††††††††††††† 1) chemical messenger
††††††††††††††††††††††† 2) transducer
††††††††††††††††††††††† 3) effector
††††††††††††††††††††††† 1) leak channels
††††††††††††††††††††††† 2) gated channels
††††††††††† Channel opening and closing:
††††††††††††††††††††††† 1) binding of a chemical messenger to a receptor
††††††††††††††††††††††† 2) changes of membrane electrical status
††††††††††††††††††††††† 3) stretching or other mechanical deformation
††††††††††† Chemically gated channels
††††††††††††††††††††††† 1) in nerve and muscle cells
††††††††††††††††††††††††††††††††††† a) chemically gated Na+ channels
††††††††††††††††††††††††††††††††††† b) chemically gated K+ channels
††††††††††††††††††††††† 2) in some cells transient flow of Ca2+
The selectively permeable plasma membrane
††††††††††† Properties of particles determine permeability of the membrane:
††††††††††††††††††††††† 1) lipid solubility
††††††††††††††††††††††† 2) size
††††††††††† Forces involved in accomplishing transport across the membrane
††††††††††††††††††††††† 1) passive forces
††††††††††††††††††††††† 2) active forces
Fickís law of diffusion
††††††††††† Factors determining the rate of net diffusion
††††††††††††††††††††††† 1) magnitude of concentration gradiet
††††††††††††††††††††††† 2) permeability of the membrane
††††††††††††††††††††††† 3) surface area of the membrane
††††††††††††††††††††††† 4) molecular weight of the solute
††††††††††††††††††††††† 5) distance
Electrochemical gradients †††
††††††††††† Ions diffuse along their electrical gradients as well as their concentration gradients. The net effect is an electrochemical gradient.
1. Voltage is defined as the measure of potential energy that exists between separated electrical charges of opposite sign; the greater difference in charge between 2 points, the higher the voltage; the voltage is often called the potential difference or potential between 2 points).
2. Electrical voltage gradients, called membrane potentials, exist across all cell membranes. Membrane potentials result from the difference in charge between the cytoplasm & the extracellular fluid. Membrane potentials depend on the different concentrations of ions (charged atoms/molecules) on either side of the cell membrane.
3. Neurons & muscle cells are excitable cells; they are able to respond to a stimulus by changing their membrane potential to conduct signals; a change in membrane potential depends on the movement of ions across the membrane.
4. Nerve impulses then are electrical signals created by the movement of ions across the neuron cell membrane in response to some stimulus.
5. Due to the nature of the phospholipid bilayer, ions must cross cell membranes by way of specific ion channels, constructed of membrane proteins. (If they tried to go through the phospholipid molecules, they would get "stuck" in the fatty acid tails.)
CELL MEMBRANE ION CHANNELS
Cell membrane ion channels are constructed of membrane proteins and are very selective. When ion channels open, ions diffuse quickly across the membrane following their electro-chemical gradients, creating electrical currents and voltage changes across the membrane; ions move along chemical gradients when they diffuse passively from an area of higher concentration to an area of lower concentration; ions move along electrical gradients, when they move toward an area of opposite electrical charge.
"Leaky" or Passive Channels - these channels are always open
"Gated Channels" - controlled by proteins that can change shape to open or close the channel in response to various signals. The signals include: voltage, chemical, mechanical, and light.
1. Voltage gated channels- open and close in response to changes in the voltage or membrane potential; involved in generating action potentials.
1. Chemically gated channels - open and close in response to chemicals, such as neurotransmitters (ex. acetylcholine), hormones, and ions such as H+ and Ca+2; involved in generating graded potentials.
2. Mechanically gated channels - open and close in response to mechanical vibration or pressure, such as sound waves or the pressure of touch (found in sensory receptors in the skin, ear, etc.); involved in generating graded potentials.
3. Light gated channels - close in response to light (found in the eye); involved in generating graded potentials.
RESTING MEMBRANE POTENITAL
Defined:† Resting membrane potential (-70 mV) is the voltage that exists across the cell membrane during the resting state of an excitable cell (a muscle cell or neuron). The negative sign indicates the inside of the membrane is negatively charged with respect to the outside.
A. Set-up:† The resting membrane potential is set-up mainly by 1.) concentration gradients of Na+ & K+ ions, and††† 2.) the permeability of the cell membrane to those ions. ††
1. Na+ & K+ Concentrations
Extracellular - The predominant extracellular ion is Na+.
Intracellular - The predominant intracellular ion is K+.
2. Membrane Permeability - The membrane is much more permeable to K+ than to Na+; because of this difference in permeability, K+ passively diffuses out of the cell from a higher to lower concentration at a much higher rate than Na+ passively diffuses into the cell; this unequal Na+/K+ diffusion across the membrane results in a relative loss of positive ions within the cell, establishing a negative charge on the inside of the membrane and a positive charge outside the membrane. (This movement of ions involves the leaky or passive type of ion channels that are always open.)
B. Maintenance: The Na+/K+ Pump††† (the ďpumpĒ is a membrane protein)
The resting membrane potential is maintained by the Na+/K+ pump. Using ATP, the membrane bound Na+/K+ The pump actively transports Na+ back out of the cell and K+ back into the cell (if it weren't for the pump, Na+ and K+ concentrations would eventually become equal inside and outside the cell and the membrane would become electrically neutral on both sides!).††† (Remember active transport mechanisms require ATP because they are transporting against the concentration gradient.)
MEMBRANE POTENTIALS THAT ACT AS SIGNALS ††(2 kinds: Graded & Action)
[Again, neurons are able to respond to a stimulus by changing their membrane potential to conduct signals or nerve impulses!!]
Graded Potentials (also called generator or receptor potentials) (the short distance signals) - short-lived, local changes in membrane potential; the signal dissipates with distance; their magnitude varies directly with the strength of the stimulus; they are essential in initiating action potentials. Events:
1. Gated ion channels are triggered by some stimulus to open.† The appropriate stimulus opens chemical, mechanical, or light gated ion channels.
2. A small area of the membrane is hyperpolarized or depolarized.
a. If the stimulus opens Na+ channels, Na+ moving into the cell causes the membrane potential to become more positive, resulting in depolarization; the inside of the membrane becomes more positive and the outside becomes more negative. Important: We will soon learn how a graded potential that depolarizes the membrane can lead to the generation of an action potential.
b. If the stimulus opens K+ channels, K+ moving out causes the membrane potential to become even more negative, resulting in hyperpolarization. Important: This kind of graded potential can prevent the generation of an action potential (it has an inhibitory effect). It actually causes the membrane to drop below resting membrane potential so that itís impossible to get to threshold potential to generate an action potential. Itís kind of like trying to make baskets with a basketball when you are down in a 20-foot pit. You could make a basket when you were at ground level, but now that you are in this pit, itís impossible!†
3. †The magnitude of a voltage change is proportional to the strength of the stimulus. The stronger the stimulus, the more gated ion channels that open and the greater the depolarization or hyperpolarization.
Action Potentials (the long distance signals) - do not decrease in strength with distance; in neurons, a transmitted action potential is called a nerve impulse; it involves the opening of voltage gated ion channels located on axons. Events:
1. Generation of an Action Potential (Depolarization) results from an increase in sodium permeability and reversal of membrane potential. If a stimulus is strong enough, a graded potential will causes the membrane to depolarize to a certain level, called threshold (usually between -55 mV & -50 mV). This causes voltage gated Na+ channels to open. Na+ rushes into the cell, driven by electrochemical gradients. As more Na+ enters, the voltage changes further and more voltage gated Na+ channels open. The membrane potential depolarizes to +30 mV.
Decrease in sodium permeability - Voltage gated Na+ channels close after a few milliseconds of depolarization.† The entry of Na+ declines.
Increase in potassium permeability - As Na+ entry declines, voltage gated K+ channels open and K+ rushes out of the cell, following its electrochemical gradient. As K+ leaves, the cell interior becomes less positive (more negative) and the membrane potential moves back toward the resting level; this is called repolarization.†
3. Hyperpolarization - The outflow of K+ during repolarization may be large enough that temporary hyperpolarization of the membrane may occur, producing a voltage more negative than the resting membrane potential (-90 mV). This is called the undershoot on a graph of the action potential. As voltage gated K+ channels close the membrane potential returns to the resting level.††††††
4. Propagation of the Action Potential - As Na+ flows in and depolarization increases, the depolarization opens voltage gated Na+ channels in adjacent sections of the membrane (this process is similar to what occurs in graded potentials) and the events described above are repeated. Consequently, the process is repeated continuously along the length of the axon, each section of the axon triggering the depolarization of the section adjacent to it. The traveling action potential is the nerve impulse!
5. The "All or None" Principle - Once an action potential is generated (once threshold is achieved) in a neuron, the nerve impulse is propagate regardless of the strength of the stimulation.
6. Hyperpolarization - Donít forget that stimuli donít always depolarize the membrane - they can also hyperpolarize the membrane. Hyperpolarization will not result in the generation of an action potential. If the membrane is hyperpolarized below resting membrane potential, it will be impossible for the membrane to reach threshold potential to open the voltage gated channels.†
How do we know all of this is going on in a neuron?† The electrical properties of a neuron can be studied by inserting a microelectrode into its interior.† A recording instrument called an oscilloscope will record the changes in membrane potential as an impulse sweeps past the intracellular electrode.