Excitable Cells

Question 1

Excitable Cells

Answer 1

One major way in which cells communicate is through activation of excitable cells. Excitable in this context refers to the generation of an electrical current that can be propagated along the cell membrane. Only neurons and muscle cells do this, but there’s also evidence that this may occur in glial cells.

All cells have ion channels in the membrane. The movement of ions through them establishes flow of current across the membrane. Excitable cells differ because this current can be propagated along the cell membrane. The formation of a propagating current requires the presence of specific ion channels, with unique properties, in the cell membrane and ion concentration gradients across the cell membrane.

This propagating electrical current is known as an action potential.

Question 2

Neuron

Answer 2

A critical component of cell-cell communication pathways that transfer info throughout the body. Capable of receiving stimuli (energy in form of light, sound, chemicals, or proteins) and altering their membrane properties to form electrical currents (represented by graded and action potentials).

The term potential refers to ability of current flows to carry out work. Membrane potentials generate currents that enable neurons to transmit info to other cells, and thereby regulate homeostasis. Info, in form of wide variety of stimuli, impacts neurons and elicits a graded potential, which, in turn, can elicit an action potential.

The action potential generates a current that travels the neuron cell membrane to its terminus. The gap between them is called a chemical synapse. Neurotransmitters are released.

Question 3

Electrical Synapse

Answer 3

In some cases, the axon makes direct contact with another cell to form an electrical synapse. Current flows directing from one cell to another through gap junctions. These release of neurotransmitters or direct initiation of another current is the means by which an action potential transmits info from one cell to another.

Question 4

Neuron: Cell Body

Answer 4

Similar to other cells, but has extended membrane processes called dendrites and axons, and can project as a single or branched process. The nucleolus contains large amounts of euchromatin (uncondensed chromosomes) and very little heterochromatin (condensed chromosomes). Metabolically active cells that synthesize large amounts of protein have large amounts of euchromatin. Within the neuronal cell body, filaments separate areas of rough endoplasmic reticulum known as Nissl bodies. They’re the sites of extensive protein synthesis. The majority of protein synthesis occurs in the cell body, less occurs in dendrites, and none occurs in the axon.

Proteins and other materials are transported from cell body to ends of both dendrites and axons, as well as back to the cell body.

The neuronal cell body also has an extensive Golgi apparatus surrounded the nucleus, with many mitochondria and other cell organelles.

Question 5

Neuron: Dendrites

Answer 5

Thin membrane projections that have a greater diameter than axons. Filled with small amounts of cytoplasm and contain numerous ribosomes.

Many are decorated with thousands of even tinier projections called dendritic spines. They contain a wide variety of ligand-gated and voltage-gated ion channels.

Functionally, dendrites integrate info received from other neurons or sensory receptors and transfer that info info in form of electrical currents through the membrane.

Question 6

Neuron: Axons

Answer 6

In most neurons, a single axon arises from a cone-shaped area of the cell body called the axon hillock. The beginning of the axon is termed the initial segment, also known as the trigger zone because of the high density of voltage-gated Na+ channels. An axon can be a single membrane projection or a branch that forms collateral axons or side branches. At the end of the axonal membrane, the membrane branches and forms enlarged ends that lie close to other cells and form synapses. Info is transferred from the axonal membrane to other cells by neurotransmitters or electrical currents.

In many cases, the axonal membrane is myelinated, covered by additional layers of cell membrane produced by nonneural cells. There’s a great deal of retrograde and anterograde transport to and from the cell body. Proteins, organelles, vesicles, and other components are transferred through the axon. Damaged organelles, recycled membrane, and substances taken up by endocytosis in the dendrite are transported toward the cell body. Many infectious agents are transferred to the CNS from peripheral nerves by retrograde transport.

Question 7

Myelin Sheath

Answer 7

Schwann cells and oligondendrocytes are neuroglial cells that extend their cell membrane to wrap tight around the outside of the axonal membrane. The cytoplasm of the Schwann cells or oligodendrocytes is squeezed out, leaving only layers of lipid bilayer. The neuroglial cell membrane that surrounds the axon is known as myelin.

Myelin acts as an electrical insulator by increasing electrical resistance by a factor of 5K and no current flows through a myelinated portion of a membrane. A single Schwann cell can cover 1 mm of an axon, and because some axons can be 1 m in length, the myelin sheath consists of many cells. between adjacent Schwann cells (not glial) and oligodendrocytes, are non-myelinated gaps called nodes of Ranvier.

Question 8

Synapse

Answer 8

The establishment of precise connections between neurons and specific target cells is critical to nervous system function. During development, these connections form, mature, stabilize, or are eliminated by process that requires intimate communication between neurons and their target cells. The end of the axonal membrane swells to a budlike structure in close contact with another cell.

The synapse has two parts. The axonal membrane terminus is the presynaptic membrane, and the membrane of the other cell is the postsynaptic membrane.

Two types of synapses, chemical and electrical.

Question 9

Chemical Synapse

Answer 9

Asymmetrical; the presynaptic and postsynaptic membranes have different structures and functions. The presynaptic cell is characterized by presence of vesicles filled with neurotransmitters and other chemicals. They’re closed to the membrane in the synapse. In contrast, the postsynaptic cell has no vesicles but many receptors and associated proteins at the membrane.

The presynaptic cell’s action potential causes neurotransmitter release.Empty vesicles are filled with neurotransmitters by active transport in the presynaptic membrane and then dock with proteins present in the presynaptic membrane known as SNARE (soluble N-attachment protein receptor) proteins. After docking the vesicles mature in a phosphorylation-dependent process. In the presence of calcium, the vesicle fuses with the presynaptic membrane, and the neurotransmitters released into the synaptic cleft. The empty vesicle is recycled within the cell and refilled with neurotransmitter with the whole process occurring in less than a minute.

The presynaptic vesicles are filled with neurotransmitters, neuromodulators, and other chemicals. Neuromodulators don’t directly induce membrane currents but modify neuronal biochemical functions to increase or decrease the likelihood that a membrane current will be generated in the postsynaptic cell. Neurotransmitters are released in a quantal (in a specific number) fashion because each vesicle releases all of its neurotransmitters, and each has approximately same # of vesicles.

Once the neurotransmitters are released at the presynaptic membrane, they rapidly diffuse across the synaptic cleft to the postsynaptic membrane, where they bind to specific membrane receptor proteins. The interaction with these receptors leads to either

1) opening or closing of ion specific channels (iontropic)
2) a biochemical alteration in postsynaptic cellf unction (metabotropic)

Question 10

Iontropic Pathway

Answer 10

opening or closing of ion specific channels

Responds more quickly to neurotransmitters, has no biochemical amplification and are either excitatory or inhibitory.

Question 11

Metabotropic Pathway

Answer 11

a biochemical alteration in postsynaptic cellf unction

Responds more slowly to neurotransmitters, has biochemical amplification, and are either excitatory or inhibitory.

Question 12

Chemical Synapse: Info Flow

Answer 12

1) An action potential depolarizes the axonal membrane. The depolarization of the membrane results in an inward Ca+2 current.
2) The influx of Ca+2 results in the fusion of neurotransmitter-containing vesicles with the cell membrane.
3) Vesicle fusion results in the opening of vesicles to the synaptic cleft and the release of neurotransmitters.
4) Neurotransmitters (and neuromodulators) diffuse across the synaptic cleft where they interact with specific membrane receptors.
5) Neurotransmitter binding to membrane receptors initiates a postsynaptic membrane current or causes a biochemical change within the postsynaptic cell.

Question 13

Electrical Synapse: Gap Junction

Answer 13

The gap junction is composed of sets of channels. Each channel is made up of six protein subunits called connexins. The entire set of six subunits together is called a connexon. Two connexons, one in presynaptic membrane and one in postsynaptic m, make up a gap junction.

The gap junction allows the action potential in one cell to move rapidly into the other, without a delay inherent in chemical synapses. Electrical is fast but can’t be modulated (changed), so they only occur where speed is paramount. ES’s are found in cardiac muscle and in smooth muscle where it’s important to coordinate the activities of a large # of cells. Because the current flows in both directions, they don’t have dedicated presynaptic and postsynaptic membrane (both cells can function as either).

Question 14

Neurotransmitters

Answer 14

They can be composed of amino acid derivatives, peptides, proteins, amines, gases, and other chemical ligands. They can either stimulate or inhibit postsynaptic cells.

Agonists are chemicals that can act like neurotransmitters, but they block the effects of them instead. Agonists and antagonists work by interacting with the neurotransmitter receptor.

Question 15

Electric Current Formation

Answer 15

Although the osmolarities of the neuronal extracellular and intracellular fluids are the same (each side has same # of solutes per volume), the solute compositions are not the same. Extracellular contains more Na+, Ca+2, and CL- than the intracellular fluid, which has more K+. Because energy can’t be created or destroyed, but just changed form, this distribution represents potential energy to carry out work.

The intracellular fluid is slightly negative relative to extracellular fluid. The membrane potential can be used to drive the flow of ions across the membrane.

Question 16

Membrane Ion Channels

Answer 16

The neuronal cell body has ligand-gated ion channels, dendrites have ligand-gated and voltage-gated ion channels, and axons have voltage-gated ion channels. Muscle cells also have both.

Question 17

Leak Channels

Answer 17

Cell membranes also contain nongated ion (or leak) channels, which are always open and allow ions to selectively flow through the membrane at rest and stimulated.

Leak channels are ion selective, not ion specific. An ion selective channel will allow for passage or several ions, but one with a much higher conductance. An ion-specific channel will only allow for passage of a single ion, regardless of the concentration of other ions.

The density and nature of membrane leak channels determine the conductance of the resting plasma membrane to ions. At rest, the neuronal cell membrane is much more permeable to K+, less so to Cl-, and very impermeable to Na+. This means that the neuronal cell membrane has leak channels for K+, but fewer or none for Cl- and Na+.

Question 18

Ligand-gated Ion Channels

Answer 18

Cell membranes also have ligand-gated channels that open in response to the specific chemical ligand (neurotransmitters). These channels and rapidly change cell membrance confuctance. Chemical ligands, including neurotransmitters, bind reversibly to a cell surface receptor molecule that, in turn, alters the properties of a cell membrane ion channel. Ligands can open or close specific ion channels. Some ligands bind to different receptors and can stimulate or inhibit a target cell, depending on the type of receptor in the target cell membrane.

Question 19

Voltage-Gated Ion Channels

Answer 19

Another type of ion channel. Opens and closes in response to small voltage changes across the cell membrane. These channels open from the inside of the neuron because of changes in membrane voltage, in contrast with ligand-gated channels that open in response to the presence of ligand on the outside of the membrane.

Voltage-gated ion channels specific to K+ and Na+ are common channels in neuronal cell membranes. Ca+2-specific voltage-gated ion channels are found in smooth and cardiac muscle.

Question 20

Electrochemical Potential

Answer 20

Na+ concentration is much greater outside the cell, while K+ is greater inside. The movement of Na+ and K+ down their concentration gradients is affected by the fact that they both carry a charge. Like charges repel and opposite charges attract.

If a Na+ channel opened in a cell membrane, Na+ with its positive charge would enter the cell because of its concentration gradient and attraction of the slightly negative charge inside the cell. But its entry would be slowed and then stopped by the accumulation of positive charges inside the membrane because of like charge repulsion.

Eventually, an electrochemical equilibrium would be reached when the chemical diffusion of Na+ down its concentration gradient was balanced by electrical repulsion of like charges on the inside of the cell membrane. At the electrochemical equilibrium point, there’ll be no net movement of Na+ across the membrane even if ion channels are open.

Question 21

Membrane Resting Potential

Answer 21

Ranges from -60 to -70 mV. This membrane potential is dependent on ion concentration gradients and ion permeabilities across the membrane (remember that this is dependent on the presence of leak channels). Permeability is equivalent to conductance but is used to describe movement of charged and non-charged solutes across the membrane. Conductance only refers to movement of ions across the membrane. Membrane permeability refers to the ease by which an ion can pass through the membrane, while conductance is ability of the same ion to carry current across the membrane.

The interior of the cell is filled with negatively charged ions that cannot normally pass through the membrane, such as negatively charged phospholipids and proteins, which act to draw K+ into the cell and maintain the Vm. This difference in distribution of Na+ and K+ across the membrane is maintained by activity of a membrane protein, Na+/K+. ATPase, which uses ATP to pump three Na+ out of the cell whereas it brings in two K+. The energy expended by the Na+/K+-ATPase is the energy used to generate the membrane potential.

Question 22

Graded Potentials

Answer 22

The binding of neurotransmitters to receptors associated with ligand-gated Na+ channels in the dendrite and neuronal cell body membrane can result in the opening of these channels and the generation of an inward-flowing positive current. An inward positive current acts to depolarize the cell interior by making it more positive. The positive current is dependent on the amount of ligand binding to its receptor, because that determines how many Na+ channels are open and is, therefore, known as a graded potential. When more ligand binds a greater positive current occurs because more channels will be opened. So the change in positive charge across the membrane can vary across a wide range. As the positive current enters the cell, Na+ ions spread through the cell interior. The movement of positive ions inside the cell membrane is passive, and the change in membrane potential decreases farther away from the opened channel. The + charge spreads along the path of least resistance. There’s a resistance to + charge flow along the inside of the membrane (RL) and through the cytoplasm (RM), but the passive movement of positive charge is favored along the inside of the cell membrane because RL is less than RM. If the flow of + charge is sufficient to reach the axon hillock, voltage-gated Na+ channels trigger a different type of inward Na+ current.

Graded potentials occur mainly at dendritic spines. A single graded potential at a specific dendritic spine is short-lived and is attenuated (reduced), delayed, and change as it spreads to other dendritic spines and then to the cell body. Graded potentials that occur far away from cell body become slower and broader than signals received closer to the cell body. This has an impact on ability of ligands to elicit action potentials.

Dendrites have both ligand-gated channels and voltage-gated channels (less than that found in axon). The ion channels are not uniformly distributed over the dendritic surface. As a result, dendrites not only produce graded potentials that travel to cell body, but also produce action potentials that travel to cell body. Action potentials can also travel from cell body to dendrites. Dendritic action potentials allow current flow to reach the hillock w/o attenuation (loss of current flow).

Question 23

Action Potential

Answer 23

In the Hodgkin cycle, initial membrane depolarization must surpass threshold to activate voltage-gated Na+ channels. The axonal cell membrane has these channels, in contrast with the ligand-gated and voltage-gated ion channels in the dendrite and cell body membrane. If a sufficient Na+ current enters the dendrites, a + charge will diffuse to the hillock, opening voltage-gated Na+ channels located there. This results in the formation of an action potential. It’s not graded because its characteristics don’t vary with the # of ligand present. An action potential is known as an all-or-none response.

The action potential is a self-propagating inward Na+ current. The electric charges that occur in the cell membrane during an action potential have a characteristic structure because of the types and properties of ion channels found in the axonal membrane and the concentration gradients for those ions.

Question 24

Generation of an Action Potential: Step 1

Answer 24

1) The axonal membrane is at rest, voltage-gated Na+ channels are closed (GNa=0), and the K+ leak channels are open. A small # of Na+ enters through K+ leak channels.

Question 25

Generation of an Action Potential: Step 2

Answer 25

2) The arrival of positive charge at the hillock alters the permeability of the membrane to Na+ as voltage-gated channels are activated. An inward Na+ current enters the membrane and depolarizes the inner axonal membrane. Locally, the Vm is no longer -70 mV but is changing to 65 mV. GNa is not 0, and the K+ leak channels are still open and carry positive charge out of the cell. This is graded depolarization to threshold.

Question 26

Generation of an Action Potential: Step 3

Answer 26

3) The inward Na+ current acts in a positive feedback manner to open additional channels, which increases the inward positive current, increases the opening of additional channels, and so forth. The K+ leak channels are still open and carry + charge out of the membrane (remember that the K+ equilibrium potential is -101 mV and as the Vm becomes more positive, the force acting on K+ is increased). The threshold point (-55 mV) is the point at which the action potential cannot be prevented from occurring because the inward Na+ current is greater than the outward K+ through the leak channels and the membrane is rapidly depolarized.

Question 27

Generation of an Action Potential: Step 4

Answer 27

4) Voltage-gated Na+ channels are rapidly opening in the axonal membrane and the membrane interior is rapidly depolarizing. As the Vm approaches 30 mV, two changes occur in the membrane: voltage-gated Na+ channels become inactivated, and voltage-gated K+ channels are opened.

Question 28

Generation of an Action Potential: Step 5

Answer 28

5) At this point, voltage-gated Na+ channels have been inactivated (absolute refractory period) and the interior of the membrane is no longer being depolarized, even though the equilibrium point for Na+ hasn’t been reached (56 mV). The absolute refractory period extends through 6 and 7. THe opened voltage-gated K+ channels (known as rectifier channels) now carry + charge out of the cell, because the K+ equilibrium point is -101 mV. During the absolute refractory period it’s not possible to initiate a second action potential because it’s impossible to active the voltage-gated Na+ channels.

Question 29

Generation of an Action Potential: Step 6

Answer 29

6) Voltage-gated K+ channels carry positive charge out of the membrane and the interior begins to repolarize (become more negative). Positive charge in the form of K+ exits the interior until approximately -80 mV, when the voltage-gated K+ channels are inactivated.

Question 30

Generation of an Action Potential: Step 7

Answer 30

7) Voltage-gated K+ channels are still carrying positive charge out of cell as cell approaches resting potential. Voltage-gated Na+ channels are moving from an inactivated state to a closed state.

Question 31

Generation of an Action Potential: Step 8

Answer 31

8) As the membrane goes into the after-hyperpolarization phase, which is due to the higher than reseting membrane permeability to K+ (caused by the slow opening of voltage-gated K+ channels) the cell becomes slightly depolarized because of a Na+ leak current. It’s now possible to initiate a new action potential. However since the membrane is hyperpolarized, it’s further from threshold at rest and it will take a larger stimulus to reach threshold than it does at rest putting the cell in the relative refractory period.

Question 32

Generation of an Action Potential: Step 9

Answer 32

9) Finally, the Vm has returned to resting values, the voltage-gated Na+ channels are closed, voltage-gated K+ channels are inactivated, leak K+ channels are open, and a new action potential is possible.

Question 33

Propagation of Action Potentials

Answer 33

Action potential is initiated at the axon hillock. The action potential must move from the hillock to the synapse to pass info to another cell. The action potential is propagated (carried) by the spread of the inward Na+ current that opens voltage-gated Na+ channels in the axonal membrane. The propagation of the action potential is similar to the movement of a wave onto a beach. At the crest of the wave, voltage-gated Na+ channels are opened, whereas at the wave trough, voltage-gated Na+ channels are inactivated and voltage-gated K+ channels are opened. At the front of the wave, the voltage-gated Na+ channels are just starting to open.

The fact that the voltage-gated Na+ channels are refractory to reopening until the cell interior has returned to Vm means that the action potential must propagate away from the cell body toward the end of the axon. If the action potential was initiated in the midpoint of the axon, it could spread in both directions.