The nervous system This system is highly developed and it is responsible for monitoring the external environment, i.e. it is trying to maintain homeostasis ( the maintenance of a constant internal environment despite external changes). The nervous system is split into the central nervous system/CNS which is composed of the brain and the spinal cord-where the decision making of a stimulus ( a change in the internal/external environment) is made and the peripheral nervous system/PNS- made of nerves (bundled by connective tissue) going in and out of the CNS. The functional unit of the nervous system is a neurone/ nerve cell. There are three types of neurones:1. Sensory/afferent neurones- these neurones carry impulses into the CNS 2. Interneurons/ intermediate neurones/ relay neurones- these neurones only exist in the CNS and pass impulses to each other in the CNS and to motor neurones. 3. Motor neurones/ effector neurones/ efferent neurones- these carry impulses to the effector organs- almost always to a muscle or a gland. These are then made to respond to a stimulus. The resting membrane potential This is so called because it occurs at the membrane and it is also sometimes called the resting potential. Any resting cell will have this potential ( a charge difference which results in an energy difference, also called a voltage) , a value of around -70mv- an unequal distribution of charges across the membrane, where the inside more negative relative to the outside. In this state, the membrane is said to be polarised. This potential is achieved by a number of channel proteins and a cation pump/ carrier protein /intrinsic protein called the sodium ion and potassium ion ATPase( sometimes called the sodium ion and potassium ion pump). When measuring an action potential, the charge excess of the inside is looked at rather than the outside, so the word relative is important. How the resting membrane potential is achieved In the plasma membrane/ neurilemma of the neurone, there are sodium ion channel proteins and potassium ion channel proteins embedded. There are more potassium ion channel proteins than sodium ion channel proteins, hence why the membrane is more permeable to potassium than sodium. This is important in the establishment of the resting membrane potential- as in the resting potential, the resting membrane potential is much closer to equilibrium potential of potassium ions than the equilibrium potential of sodium ions. Equilibrium potential means the voltage across the membrane when equilibrium for a particular ion is established and the resting membrane potential is the sum of all the equilibrium potentials of contributing ions ( mainly sodium and potassium ions). The sodium ion and potassium ion pump starts off the resting membrane potential. This pump , using ATP hydrolysis( which provides energy), pumps out 3 sodium ions out for every 2 potassium ions in. This establishes a concentration gradient for both ions. Sodium ions want to go in the cell and potassium ions want to go out. Potassium ions are able to go out as there is more channel proteins embedded for potassium than sodium and so many go back in down a concentration gradient. However, there is an electrical gradient due to more negativity on the inside( because of the negative anionic proteins in the cytoplasm/axoplasm) compared to the outside and so potassium ions, as well as sodium ions will try and balance this . This double gradient (the concentration and electrical gradient) is called an electrochemical gradient. As soon as this balance has been achieved, a resting membrane potential has also been achieved. The sodium ion and potassium ion pump continuously pumps out sodium ions and potassium ions in their respective directions and so maintains a resting membrane potential with the events recurring all the time. Note that are two things which are key in establishment of a resting membrane potential, these are: The sodium ion and potassium ion pump- this pump is referred as being electrogenic. This means that it is involved in the creation of the resting membrane potential. This is true as this pump is the cause of the concentration gradient , electrical gradient and thus the resting membrane potential. Remember , always a concentration gradient will follow an electrical gradient. The permeability- potassium ions are more permeable than sodium ions in the creation of this membrane potential as if both the key ions , sodium and potassium ions, had equal permeability, there wouldn’t be a resting membrane potential as the gradients would equalise. (By the way in some cells, particularly nerve cells, chloride ions are also important the creation a resting membrane potential, where there is a chloride pump involved, but this forms a minority of cells in humans. The most important are the sodium and potassium ions). The action potential This is the way of communication in neurones to the CNS and not many cells are capable of conducting an action potential. An action potential is reverse of polarity- i.e. the temporary depolarisation of the membrane ( positive inside, negative outside compared to positive outside, negative inside in the resting potential). An action potential is also called a nerve impulse or a nervous impulse but action potential is the proper term. The action potential doesn’t last that long, about 3 to 4 milliseconds(ms) and the resting state is quickly restored by the action of the pump. How the action potential is created The action potential propagation across the body starts off with a stimulus in the PNS. A sensory receptor is able to transduce, in other words convert this stimulus information e.g. sound vibrations recognised by the organ of Corti into an action potential. This then stimulates a neurone by opening up some of the voltage gated sodium ion channel proteins. These sodium ions are able to go in now down their electrochemical gradient(as both gradients favour sodium going in because its more negative inside compared to the outside and also sodium ions are more concentrated on the outside than inside). What these sodium ions do now is that they diffuse sideways from an area of slight positivity (i.e where the sodium ions enter) to an area that is slightly negative. And so by doing that, they activate voltage gated sodium ions and so more sodium ions are able to go in. This increases the permeability of sodium ions. Once a value of around -55mV is reached, known as the threshold( level/potential/value), an action potential will occur. Events before this are known as generator potentials. Whether or not an action potential is reached is dependent on the stimulus. If the stimulus is strong, it is able in opening even more sodium ions and so an action potential will be fired. But if the stimulus is weak, there is a chance that a resting potential is restored as not many sodium ions aren’t able enough to get a value of -55mV. This is known as the all or none theory. If an action potential is initiated , nothing can stop it and now we get a depolarisation of the membrane with even more sodium ions going in a positive feedback mechanism. i.e. if more sodium ions go in, they are able to cause the opening of the voltage gated sodium ion channels and that means more sodium ions are able of going in and so on. This activity causes the conductivity of sodium ions inwards to be greater than potassium ions. After this, a value of around +30mV is reached as the Ek of sodium is being reached. During this time of increase sodium ion conductivity, we get the slow activation of other voltage gated channels called the voltage gated potassium ion channel proteins. This is why in the graph above there is a slight dip rather a straight spike. Once the activation occurs, this is simultaneously accompanied by the inactivation of the voltage gated sodium ion channels. Now potassium ions are able to go out down their electrochemical gradient and start causing a repolarisation-this essentially means getting a value close to that of the polarised membrane. With more potassium ions going out, there is a slight undershoot as these ion channels are inactivated and so this is now called hyperpolarisation-i.e. more polarised than at the resting level. This brief period is called the relative refractory period, which quite simply means that you must have a stimulus so strong in order to able to cause the action potential in the region of the neurone it just occurred. This is different to the absolute refractory period. In this period, which is for most of the action potential except this relative refractory period, an action potential cannot occur in the same region as it was just happening even though how strong the stimulus is. A resting state is reestablished by the action of the sodium ion-potassium ion pump. Propagation of the action potential In an neurone that is unmyelinated, that is it isn’t covered by myelin ,a lipid , on the plasma membrane, there are short local circuits/currents. An action potential is able to propagate in a neurone because throughout it, there are voltage gated sodium ion channel proteins able to conduct sodium inwards. And so we get the same events repeating itself again and again. However, a neurone with a myelin sheath, there are longer local circuits. This is essentially the same as with unmyelinated neurones but because lipids are hydrophobic, they don’t conduct sodium ions inwards as it would be impermeable. So there is a “jump” effectively to a region that remains unmyelinated and so get an action potential occurring at the nodes of Ranvier i.e. the gaps between the myelin sheath. This is referred to as saltatory conduction. This increases the velocity(speed/time) that a neurone is able to conduct an action potential and so information is able to get to the CNS quickly and therefore get a response which is much faster. In general, a neurone which is longer in diameter and is myelinated will give the fastest action potential propagation. A longer diameter can mean two things ; (1) that either there are less synapses, so less delay (2) or it can mean that there is a larger area and some more sodium ions are able to get inside and speed up opening of the voltage gated channel proteins. Other factors such as temperature can increase the velocity of the conduction of the action potential. This is because increasing temperature can increase the kinetic energy , thus speeding up the facilitated diffusion of the channel proteins. In the PNS, Schwann cells form a myelin sheath but the CNS ,astrocytes form a myelin sheath. These cells are examples of glial cells. Glial cells gives neurones nourishment to the cells, act as macrophages etc. and actually constitute up to 90% of the cells in the CNS. Furthermore, neurones would be nothing without them. The synapse This is anatomically defined as being a gap between two neurones. There are in general two types of synapses:1. Chemical synapse- where there is in fact actual gap between two neurones and the neurones have to secrete a substance known as a neurotransmitter . This is a form of cell signalling and is common in the PNS. 2. Electrical synapse- where there is no real gap but is connected through proteins known as gap junctions/connexons . These are found in cardiac muscle cells, an electrically excitable cell. The chemical synapse The action potential reaches a pre-synaptic neurone. The change in voltage that occurs will activate the voltage gated calcium ion channel proteins. Due to the concentration and electrical gradient, calcium ions flow down by an electrochemical gradient through Prethese channel proteins by facilitated diffusion. These synaptic calcium ions bind to vesicles containing a neurone neurotransmitter e.g. Acetylcholine, often abbreviated to ACh. The neurones that secrete ACh are called cholinergic neurones and where it is released is therefore called a cholinergic synapse. Now, vesicles Post-synaptic containing this neurotransmitter will fuse with the neurone plasma membrane , release ACh (not the vesicle)by exocytosis into the synaptic cleft/gap and diffuses through this 20nm gap. ACh will bind to a complementary protein receptor located on the post-synaptic neurone , called a nicotinic/ muscarinic receptor proteins dependent where in the body it is found. What happens from now will depend on the type of channel activated. Some neurotransmitters will cause the direct activation of an ion channel protein associated to the complementary receptor, mainly conducting sodium ions inwards . These receptors that this neurotransmitter binds to is therefore known as an ionotropic receptor. Other receptors will cause activation of G-proteins once a neurotransmitter. These receptors are therefore called G-protein coupled receptor (GPCR’s) or metabotropic receptors. Gproteins once activated might cause an ion channel to be open directly or indirectly through activating enzymes-a process of signal transduction. Once ion channels are activated they could either cause an action potential to occur so called an excitatory synapse and the potential that is created is known as an excitatory post-synaptic potential or EPSP or it is called a generator potential . However, it could also actually inhibit action potential formation and so is called an inhibitory synapse and the potentials that are created are known as inhibitory post-synaptic potential or IPSP. Dependent on what occurs next, you get action potential formation by EPSP’s and so propagates through the next neurone OR the action potential can actually stop there by IPSP’s. The latter case occurs mainly in the CNS. You don’t want action potentials to be propagated all the time and so there is an enzyme called Acetylcholine esterase (ACh esterase) that will break down ACh into acetate and choline. Choline is taken up back into the synaptic (knob/bulb/terminal) and so stop therefore an action potential from occurring. Mitochondria are needed in the synaptic knob so that ACh can be formed as acetate will be obtained from the( Krebs/TCA/Tricarboxylic acid) cycle . This obviously will require some ATP. Disadvantages of synapses 1. In the chemical synapse, the velocity of the action potential is slowed as it is reliant on how fast the neurotransmitter diffuses across the gap. 2. The synapse can be affected by chemicals/drugs. E.g. nicotine. Nicotine can bind to nicotinic ACh receptor proteins and instead of causing an action potential, it will inhibit ACh from binding and so will not allow an action potential to propagate. 3. Can have competitive or non- competitive inhibitor activity on ACh esterase. This means that the enzyme cannot function and so constant action potentials can be propagated and eventually lead to desensitisation of the synapse. 4. Can have something that affects the voltage gated calcium ion channel proteins, so this means there cannot be release of the neurotransmitter in the synaptic cleft. Advantages of synapses 1. It means that the action potential is unidirectional. There are two reasons for this: Receptor proteins for the neurotransmitter are on the post-synaptic neurone Vesicles containing the neurotransmitter are in the synaptic knob/ pre-synaptic neurone 2. Allows inhibition of some reflexes. 3. Permits learning and memory. 4. Allows acclimatisation- the point where something bothering you for example doesn’t. 5. Allows convergence- several post -synaptic neurones acting on one post-synaptic receptor 6. Allows divergence-one pre-synaptic neurones will act on many post-synaptic receptors. 7. Allows temporal and spatial summation. I.e. the addition of action potential effects to make a post-synaptic neurone propagate or inhibit an action potential. Spatial summation is the addition of impulses from different neurones at the same time and temporal summation is the addition of impulses done by the same neurone at slightly different times, i.e. in succession of one another and therefore isn’t at the same time. Divisions of the PNS The PNS is structurally and functionally divided into the sensory and motor nervous systems. The sensory system will comprise all of the nerves that will go into the CNS. The motor nervous system is further divided into the somatic and autonomic nervous systems. The somatic nervous system controls (skeletal/voluntary/striated) muscles. The autonomic nervous system controls the viscera i.e. all the internal organs e.g. adrenal glands, stomach etc. However, there is also the enteric nervous system/ENS present as well. This is special to the (gastro-intestinal/alimentary)tract and essentially is called the gut brain. This is independent of the CNS but still is influenced by it. The ENS comprises the submucosal and myenteric nerves/plexuses. The autonomic nervous system(ANS) This is a motor nervous system controlling the viscera. This system is described as being self-minding, largely because it is independent of conscious control. E.g. the nerves that control cardiac output/CO( CO=stroke volume(SV) x heart rate (HR)) are called the accelerator nerve( a sympathetic nerve) and the vagus nerve( a parasympathetic nerve). You can’t think of when you should raise your heart rate or stroke volume for example, try it-but it will not work. So, therefore the aim of this nervous system is to maintain homeostasis. Anatomically, there are always two neurones that connect to one another to the effector organ. Where there is a connection between a dendrite of one neurone and a cell body/soma/centron or a dendrite or even an axon of the other is called a ganglion. It literally is a swelling. The neurotransmitter release at this ganglion is called ACh. However, at the effector organ the neurotransmitter is either noradrenalin/norepinephrine OR ACh if it is sympathetic or parasympathetic that is being discussed (see below). However, there are some exceptions to this rule. For example, only ONE nerve will stimulate the adrenal medulla of the adrenal glands to secrete the hormone adrenalin , neurotransmitter being ACh. This is because the adrenal medulla of the adrenal glands is just thought to being just a sympathetic ganglion. Due to this, you don’t get a neurone transmitting an impulse to the effector organ from this ganglion as the adrenal glands are the effector organs. Cells called the chromaffin cells secrete adrenalin located in the adrenal medulla of the adrenal glands. The ANS is further divided into the sympathetic and parasympathetic divisions /NS. These two systems are antagonists of each other. i.e. one system in most cases is a complete opposite of the other. They are even different anatomically. The sympathetic system has short pre-ganglionic neurones, i.e. the neurone before the ganglion and long post-ganglionic neurones which is after the ganglion. These nerves originate from the thoracic and the lumbar regions of the spinal cord and therefore these nerves also are referred as thoracolumbar nerves. Post-ganglionic neurones will secrete noradrenalin and this neurotransmitter has stimulatory effects on target organs usually. E.g. it causes pupils to dilate by causing contraction of radial muscles of the iris (therefore relaxation of circular muscles) so that eyes are ready for far vision, it essentially allows more light in and so information can go to the brain etc. Overall, this system is getting the body ready for a flight or fight response, i.e. for stressful action. The parasympathetic nervous system has long pre-ganglionic neurones and has short post-ganglionic neurones. The ganglion actually may be embedded in the target organ. These nerves originate from the brain stem and the sacral region of the spinal cord and therefore these nerves also are referred as craniosacral nerves. Post-ganglionic neurones will secrete ACh and this neurotransmitter has inhibitory effects on target organs usually. E.g. it causes pupils to constrict by causing contraction of circular muscles of the iris (therefore relaxation of radial muscles) so that eyes are ready for near vision. Overall, this system prepares the body for a rest or a digest. The somatic nervous system (SNS) This NS is a motor NS controlling skeletal muscle-i.e. the muscles of the skeleton. This muscle is an electrically excitable fibre and is able to conduct an action potential. This is important as this is the cause of muscle contraction ( getting shorter and producing force ). Unlike the ANS, the SNS can operate under conscious control. This is why the muscle is also called a voluntary muscle. You can decide for example when to move your hands, legs etc. Also, there will only be ONE neurone that will propagate an action potential to the effector organ and so there are no ganglions. The point at which a neurone is contact with a skeletal muscle fibre is called the motor end plate or the end plate. This occurs at the neuro-muscular junction (NMJ). The NMJ This junction is similar to the synapse between two neurones except in this case, we are dealing with an end plate, i.e. neurone to skeletal muscle fibre junction. The principles of the activity at the synapse are the same as with the NMJ , so you get the action potential coming the pre-synaptic neurone , this causes voltage gated ion calcium channel proteins to open and so get calcium coming in via an electrochemical gradient through this channel. This is followed by calcium ions binding to the vesicles containing the neurotransmitter ACh and so get the release of ACh out of the synaptic bulb by exocytosis into the synaptic cleft. Next, ACh diffuses through this gap and binds to a complementary receptor protein called the nicotinic receptor. This causes ion channels associated with the receptor to open which allow positive ions/cations through, mainly sodium ions through. This causes depolarisation of the skeletal muscle fibre plasma membrane/sarcolemma (an end plate potential) thus allowing for a local circuit formation across the muscle fibre. The change in voltage on the sarcolemma always permits depolarisation of the membrane and so is always excitatory, never inhibitory. The end plate is in the middle of the muscle fibre and means that we can get local circuit formation on both sides of the endplate. There are invaginations in the sarcolemma called transverse tubules/ T-tubules/T-system. This is important because this is associated with the sarcoplasmic reticulum/SR (an important calcium ion store) through a foot process. Two proteins form this foot process; one in the t-tubule membrane called a dihydropyridine/DHP receptor protein, which acts as a voltage change sensor, and the ryanodine receptor on the SR which causes the release of calcium ions to bring about contraction of the muscle. Once a voltage change is detected by the DHP receptor, we get a change in the tertiary structure of the receptor which acts on the ryanodine receptor to cause calcium ion release through it by facilitated diffusion. Calcium ions are important because they allow contraction of the muscle fibre so as long as they are in the cytoplasm/sarcoplasm,, there will be contraction.