site: binding        



                             MOLECULES  AND PROTEIN RECEPTOR SITES

theme: Binding of neurotransmitter molecules to their receptor sites can have either an excitatory effect or an inhibitory effect depending on the nature of the complex and how it affects the permeability of the membrane i.e. on the nature of the ions which move and the direction of their movement.

PROPAGATION OF NERVE IMPULSES ALONG THE NEURON TO THE SYNAPSE Nerve impulses  are propagated to the synapse in the form of packets of electrochemical pulses or 'signals'. They arrive at the synapse in bursts of so many per second - from a few at a time up to a thousand per second. if the signals are sufficiently intense they are transmitted to connecting neurons and propagated along their axons.

 Each neuron has a critical threshold for firing an incoming nerve impulse and generating a new impulse in the connecting neuron. If the threshold is lowered by the impulse crossing the synapse then the effect is 'excitatory'. If the threshold is raised then the effect is 'inhibitory'. Activity in the postsynaptic membrane is either inhibited or excited, correspondingly preventing or enhancing the propagation of new impulses along the connecting neuron.

    The transmission of impulses from one neuron to the next depends on the specific properties of the 'presynaptic impulse' - the number of electrochemical pulses reaching the synapse (the stronger the stimulus, the more pulses are generated) as well as its effect on the 'postsynaptic membrane' (whether polarization is increased or decreased).

TRANSMISSION OF IMPULSES ACROSS THE SYNAPSE Nerve impulses are electrical messages  whose transmission across the synapse is not simply a matter of their jumping across the synaptic cleft. They are first translated into... converted into... corresponding chemical messages The arrival of a nerve impulse at the synapse  triggers an increase in permeability of the membrane to calcium ions which rush into the interior of the neuron and combine with molecules of the protein 'calmodulin'. The resulting calcium-calmodulin complex produces a specific physiological response... powerful metabolic activity which activates the release of large numbers of specialized chemical transmitter molecules - 'neural transmitter molecules' or 'neurotransmitters'.

Neurotransmitters are synthesized, packaged and stored in small 'synaptic vesicles' located in the synaptic knob of the pre-synaptic neuron at the synapse.

 NEUROTRANSMITTERS ARE PROPAGATED ACROSS THE SYNAPTIC CLEFT  The transmitter molecules travel from the synaptic vesicles in the 'synaptic knob' and are released through the presynaptic membrane of the axon terminal into the fluid-filled 'synaptic space' or 'synaptic cleft'. They are propagated across the synaptic cleft to the post-synaptic membrane of the connecting neuron. Whether or not they generate a new impulse depends on the nature of their binding to the membrane of the connecting neuron. The nature of the transmitter-receptor complex alters the postsynaptic membrane in one of two ways: it lowers the threshold for initiating or 'firing' the signal - the effect is 'excitatory'; it raises the threshold for firing the signal - the effect is 'inhibitory'.

When they reach the postsynaptic membrane of the connecting neuron, the neurotransmitter molecules interact with specific protein receptor molecules known as 'receptor binding sites' or 'transmitter receptors' or 'receptors'.

RECEPTOR BINDING SITES Receptors are protein molecules specialized for the function of attracting and binding the neurotransmitter molecules. The receptor protein molecules are embedded in the semi-fluid matrix of the cell membrane with pieces sticking out above and below the surface. Many receptors have two functional components -  a  region on the surface of the receptor protein specialized  for the binding of the transmitter molecule i.e. 'receptor binding site' and a pore which is permeable to some ions and not to others i.e. 'selectively permeable pore'.

The binding site is precisely tailored to match the shape and configuration of the transmitter molecule so that the latter fits into the receptor as specifically as a lock and key.

BINDING CREATES A TRANSMITTER-RECEPTOR COMPLEX  Binding between transmitter and receptor creates a 'transmitter-receptor complex'. Formation of the complex triggers a change which alters the three-dimensional shape of the receptor protein so that the pore component is opened. This allows for the passage of ions inside and outside the cell membrane across their concentration gradients.

 Depending on the nature of the ions which move and the direction of their movement, the transmitter-receptor binding initiates a sequence of events which either inhibit or enhance the generation and propagation of new signals along the axon of the connecting neuron.  

CONTINUED TRANSMISSION OF IMPULSE DEPENDS ON EFFECT OF BINDING The continued transmission of the nerve impulse depends on the effect of binding on the pores which allow for movement of ions across the membrane... how activity at the synapse affects the permeability of the membrane and hence the small pores which allow passage of electrically charged ions through the membrane... 

BINDING IS INHIBITORY IF IT INCREASES POLARISATION The binding of neurotransmitter molecules to receptor molecules on the postsynaptic membrane is inhibitory if it closes the pores. Closing of the pores makes the membrane less permeable and prevents the passage of electrically charged ions. This results is increased polarization of the membrane. If the membrane is further polarized, it becomes stabilized near its resting value. This raises the threshold for the the generation of a new impulse and inhibits the continued transmission of the impulse to the connecting neuron. 

BINDING IS EXCITATORY IF IT DECREASES POLARISATION The binding of neurotransmitter molecules to receptor molecules on the postsynaptic membrane is excitatory if it opens the pores. Opening of the pores makes the membrane more permeable to the passage of electrically charged ions. This results in increased depolarization of the membrane. It is further destabilized and closer to the threshold for generating a new impulse and a new nerve impulse is initiated in the connecting neuron. 

   If the inhibitory input exceeds the excitatory input then a connection is not made between one neuron and the next. If the excitatory input exceeds the inhibitory input then a connection is made between one neuron and the next. Propagation along the connecting cell occurs only if excitation of the synapse exceeds inhibition.

CONTROL MECHANISM  Whether inhibitory or excitatory, binding of neurotransmitter molecules to their protein receptor sites is precisely controlled...

control of transmission is maintained by a mechanism which rapidly inactivates the transmitter molecule once it is bound to its receptor molecule.

IMPLICATIONS FOR EDUCATION  Nerve impulses are transmitted to the connecting neuron and propagated along its axon only if they are sufficiently intense. The intensity of the impulse in the presynaptic neuron must be above the required threshold to depolarize the postsynaptic membrane. If the number of incoming electrochemical pulses exceeds the critical threshold, then the incoming impulse is transmitted and propagated along the connecting neuron. Learning is a function of stimuli strong enough to influence the effectiveness of synapses in the transmission of signals from one neuron to another across the synaptic clefts. Intrinsically motivated learning produces stronger stimuli than extrinsically motivated learning... 

Intensity of stimuli is increased with 'optimalearning'...

'holistic education'