Synaptic Transmission:

Types of Synapses:

a)One to one synapse-such type of synapses are found in neuromuscular junction where an action potential in presynaptic element produces an action potential in postsynaptic element.

b)Many to one Synapse-such types of synapses are found on spinal motor neurons where many cell synapses on postsynaptic cell are required to depolarize.The synaptic input may be excitatory or inhibitory.

Excitatory postsynaptic potentials(EPSPs)

• EPSP is produced by depolarization of the postsynaptic cell membrane immediately under the presynaptic ending.
• it is excitatory because membrane potential moves towards  its threshold.
• produced as a result of increase in conductance to Na+ and Ka+.
• Na+ influx causes depolarization.
• The EPSPs at synapses between neurons are similar to the  EPSPs at neuromuscular junctions.
• Excitatory neurotransmitters include ACh,Norepinephrine, Epinephrine,Dopamine,Glutamate,and Serotonin.

Inhibitory postsynaptic potentials(IPSPs):

• It hyperpolarizes the postsynaptic cell,moving away from threshold.
• Hyperpolarization is caused by opening of Cl- channels.
• Inhibitory  neurotransmitters are glycine and GABA.

Summation at synapses:

• Spatial Summation occurs when two excitatory inputs arrive at postsynaptic neurons simultaneously and produce greater depolarization
• Temporal  Summation occurs when  two excitatory inputs arrive at postsynaptic neurons in a rapid succession.because resulting postsynaptic depolarization overlap in time,they add in stepwise fashion.

Neuromuscular Transmission

Neuromuscular junction is the is the synapse between axons of motorneurons and muscle.
Events occuring during Neuromuscular Transmission.

• when a action potential is produced in a axon it travels down towards the motor axon terminal.It depolarizes the presynaptic terminal that open Ca2+ channels and  Ca2+  ions moves into the presynaptic terminal down it's electrochemical gradient.
• Ca2+  uptake causes release of ACh into the synaptic cleft by exocytosis.
• ACh diffuse to the postsynaptic membrane,ACh bind to it's receptors which opens ligand gated  Na+ and Ka+ channels and Na+ influx occurs.
• Influx of Na+ causes local depolarization.The magnitude of depolarization produced is referred to as End Plate Potential(EPP).EPP is not a action potential,but a local depolarization.
• when the end plates depolarizes,local currents causes depolarization and action potential in the adjacent muscle tissue.
• ACh is degraded by acetylcholinestrase(AChE ) into acetyl CoA and choline on the muscle end plate.

Agents interfering Neuromuscular junction:

• Botulinus toxin-it blocks the release of ACh from presynaptic terminal.
• Curare-it binds with the ACh receptors on motor end plate.
• Neostigmine-it prevents the ACh degradation by inhibiting the AChE.
• Hemicholinium-blocks reuptake of choline into presynaptic terminal.

Membrane physiology

• cell membrane is 8-10nm thick.
• it is a lipid bilayer in which protein molecules are embedded
• bilayer of phospholipid molecules that are amphipathic, i.e. they consist of a polar,hydrophilic (water-loving) head and a non-polar, hydrophobic (water-hating) tail.

Components of cell membrane
1)Lipid component consists of four phopholipids:phosphatidylcholine (lecithin), phosphatidylethanolamine (cephalin),sphingomyelin and phosphatidylserine.cholesterol and glycolipids are also present.

• lipids that constitute bilayer are amphiphilic because of their hydrophobic (nonpolar) chains directed toward the center of the membrane and their hydrophilic (charged) heads directed outward.

• lipid components exhibit asymmetry in which  phosphatidylcholine (lecithin) and  sphingomyelin are located in outer leaflet; phosphatidylserine and  phosphatidylethanolamine (cephalin) are located in inner leaflet.
• cholesterol molecules are intercalated among the phospholipids of the membrane with its hydroxyl group at aqueous interface and remainder of the molecule within the leaflet.

2)Protein component consists of integral and peripheral protein

• peripheral proteins exhibit a looser association with membrane surfaces and can be easily disassociated from the lipid bilayer by changes in ionic strength and ph.

• Integral proteins are directly incorporated within the lipid bilayer.transmembrane proteins are integral proteinsthat span the lipid bilayer,exposing the protein to both extracellular space and cytoplasm.Many transmembrane proteins are also known as receptor proteins.

Receptor Proteins
a)Ion channel linked receptors:they include voltage gated ion channels,mechanical gated ion channels,and neurotransmitter gated ion channel.
b)G protein linked receptors:theses channels work through cAMP pathway or Calcium ion pathway
c)Enzyme linked receptors.

Intercellular Connections:

1)Tight junctions:

• are the attachment between the cell
• may be an intrercellular pathway for solutes,depending on the size, charge,and characteristics of the tight junction.
• may be Tight(impermeable),as in the renal distal tube,or Leaky(permeable), as in the renal proximal tubule and gallbladder.

2)Gap junction:

• are the attachment between the cell that permit the intercellular communication.e.g permit current flow and electrical coupling between myocardial cell.

Membrane Transport Mechanism



1)Cross membrane movement of small molecules:

• Diffusion(passive and facilitated)
• Active transport

2)Cross membrane movement of large  molecules:

• endocytosis 
• exocytosis

3)Signal transmission across the membrane:

cell surface receptors

• signal transduction
• signal internalization 

movement of intracellular receptors

4)intercellular contact and communication

Simple Diffusion:

• it's a passive movement across the membrane that does not  require any metabolic energy
• it's not carrier mediated
• it occurs down the electrochemical gradient(high conc. to low conc.)

Factors affecting the rate of Diffusion:

1) Its concentration gradient across the membrane.Solutes move from high to low concentration.

(2) The electrical potential across the membrane.Solutes move toward the solution that has the opposite charge. The inside of the cell usually has a negative charge.

(3) The permeability coefficient of the substance for the membrane. 

(4) The hydrostatic pressure gradient across the membrane. Increased pressure will increase the rate and force of the collision between the molecules and the membrane. 

(5) Temperature. Increased temperature will increase particle motion and thus increase the frequency of collisions between external particles and the membrane. In addition, a multitudeof channels exist in membranes that route the entry of ions into cells.

(6)Membrane thickness decreases the diffusion thickness.

Facilitated diffusion:

• it occurs down the electrochemical gradient(high conc. to low conc.) similar to simple diffusion.
• does not require metabolic energy so it is a passive transport.
• it's more rapid than simple diffusion
• it is a carrier mediated that require a carrier protein to tranport a molecule.

example:glucose transport in muscle and adipose tissues.

Active transport:

It is a kind of transport in which energy is required in the form of ATP.

a)Primary active transport:when ATP is used directly at the site of transportation then it's called primary active transport.e.g Na+-K+ ATPase and Ca+-ATPase present in endoplasmic reticulum.

b)Secondary active transport: 

The transport of two or more solutes is coupled.

One of the solutes (usually Na⁺) is transported “downhill” and provides energy for the “uphill” transport of the other solute(s).

 Metabolic energy is not provided directly, but indirectly from the Na⁺ gradient that is maintained across cell membranes.

If the solutes move in the same direction across the cell membrane, it is called cotransport, or symport.

• Examples are Na⁺-glucose cotransport in the small intestine and Na⁺-K⁺-2Cl^- cotransport in the renal thick ascending limb.

If the solutes move in opposite directions across the cell membranes, it is called countertransport, exchange, or antiport.

• Examples are Na⁺-Ca²⁺ exchange and Na⁺-H⁺ exchange.

Vesicle transport mechanism:

a)Endocytosis:it is the cell intake of extracellular vesicle.it may be

• Phagocytosis: it is the process of engulfing by cell.
• Pinocytosis:the substances ingested are in solution.it is the drinking if extracellular fluid.
• Clathrin-mediated endocytosis: occurs at membrane indentations where the protein clathrin accumulates.

b)Exocytosis:Vesicles containing material for export are targeted to the cell membrane.it is usually Ca+ dependent.

Membrane Potentials


Diffusion and equilibrium potentials:

• diffusion potential is the potential difference generated across the membrane due to concentration difference of a ion that is permeable to the membrane.
• amount of diffusing potential depends upon the amount of concentration gradient across the membrane.
• the charge of diffusion potential depends upon the charge on the ions that are diffusing.
• equilibrium potential is the potential when the equilibrium is achieved across the membrane so no more ion diffusion occurs.

Resting membrane potential:

• it is the potential difference across the membrane at rest.That is negative inside than outside.
• it is established by diffusion potential.
• this potential difference is mainly produced by the ions that are more permeable to the membrane.
• for example k+ ions are more permeable than Na+ ions at rest.so resting membrane potential of a nerve membrane is -70mV that is near to the K+ ions equilibrium potential of -85 mV.
• So the resting membrane potential is very sensitive to the extracellular K+ ion concentration.
• Increased extracellular K+ concentration will reduce the efflux of K+ ions causing depolarization.
• decreased extracellular K+ concentration will accelerate the efflux of K+ ions causing hyperpolarization.

Action Potential:

• it is the electrochemical fluctuation in the membrane of excitable cell and which rapidly propagate.

Phases of Action potential:

1. Depolarization:conduction of a signal across the membrane is done by a rapid membrane depolarization that changes the normal resting negative potential to a positive membrane potential.It depolarizes the membrane toward the threshold.Depolarization causes rapid opening of the activation gates of the Na+ channel.The Na+ is driven toward the Na+ equilibrium potential  of +65mV.
2. Repolarization of action potential:depolarization closes the Inactivation gates of the Na+ channel that results in closure of Na+ channels and Na+ conductance stops.depolarization slowly opens K+ channels and increases K+ conductance.

Refractory periods:

• Absolute refractory period:during this period no matter how how strong the stimulus,it can not induce second action potential.This is due to voltage inactivation of Na+ channels.
• Relative refractive period:during this period a greater than normal stimulus is required to induce a second action potential
• Accommodation:it occurs when the cell membrane is held at depolarized level such that the threshold potential is passed without firing an action potential e.g in hyperkalemia.

Propagation of action potentials:there are some factor that can affect conduction velocity.Most important factors are:

• size of an action potential
• cell diameter
• myelination
• demyelination