this lecture, second in the series of the heart, introduced the finer details of heart contraction and the nervous system's influence over it. the first broad section was about the general components of the action potential mechanism in the hearts. cardiac muscle is introduced as an intermediate between skeletal and smooth muscle, in that it has similarities to both (striations similar to skeletal, cell size similar to smooth). the general mechanism of cardiac muscle contraction and relaxation is then described; induced by the SA and AV nodes, which both produce differently shaped AP curves, and propagating throughout the atriums, ventricles, and purkinje fibers.
the molecular mechanism is described as well: Na+ channels initiate the AP and immediately deactivate. Ca2+ plays a crucial role in promoting a longer during AP and in the actual contraction mechanism. L-type channels have a plateau like permeability curve, representing Ca2+ ions flowing in for a long duration (~150ms), which keeps the AP depolarized for much longer (this is also aided by the decrease in outward K+ flux). inside the cell, Ca+ stimulates further release of intracellular calcium from the sarcoplasmic reticulum, which provides the Ca2+ that is mainly used in the muscle contraction. the actual contraction mechanism is nearly (or completely?) identical to skeletal muscle -- Ca2+ binds to troponin, etc. etc.
the nodes are looked at in further detail. the SA node is the sinoatrial node, which is the primary pacemaker of the heart, because its frequency of depolarization is the fastest. the AV node is a conducting pathway between the atria and ventricles, and is slower due to the relative lack of gap junctions, and this allows the delay in contraction between the atria and ventricles. in the nodes, AP's are initiated by fast T-type Ca2+ channels, which are not affected by Ca2+ blockers, have no long plateau (due to the lack of the slow L-type channels), and spontaneously, autorhythmically depolarize due to the actions of the "funny" Na+ channels, which are activated by hyperpolarization and K+ flux.
finally, we zoom out and look at the overall hierarchy of nervous control over the heart, which starts all the way up in the upper brain structures and trickles down to the autonomic nervous system via the sympathetic and parasympathetic neurons. the main differences between the sympathetic vs. parasympathetic control over the heart are elucidated. the sympathetic preganglionic neurons originate in T1-5 of the spinal cord and innervate the neurons in the autonomic ganglia. the postganglionic neurons project to the heart via the cardiac plexus, stimulating the beta1 receptors on the nodes and myocardium, using NE and E as neurotransmitters. the effect on the SA node is to increase heart rate while the effect on the AV node is to increase conductivity (decrease latency?). the sympathetic innervation also uses second messengers to activate the "funny" Na channels.
the parasympathetic nervous system effect on the heart starts with the preganglionic neurons, which route out to the heart via the cardiac plexus, whatever that is, and the post ganglionic neurons innervate the nodes (but not the myocardium). the receptors used are muscarinic receptors, with ACh as the NT and with plenty of ACh esterase in the receptor areas. the vagus nerve (the name of the parasympathetic nerve), by means of directly opening K+ channels on the SA node, using g-proteins but without any second messengers such as cAMP, thereby allows greater outflow of K+ and therefore a lower membrane potential, and therefore a harder time reaching the threshold potential, thereby reducing the heartrate.
Showing posts with label neurotransmitters. Show all posts
Showing posts with label neurotransmitters. Show all posts
Saturday, November 15, 2008
10.13.08 organ systems: neurotransmitters
this lecture introduces neurotransmitters and neuropeptides, the receptors that bind them, the actions they produce, and what role they play in the autonomic nervous system. the first section introduces neurotransmitters and synapse terminology, indicating that the object of focus in this lecture is the specific type of neurotransmitter and receptor that is involved in the synapse.
the second section gives an overview of the nervous system, specifically the peripheral nervous system and the distribution of neurons throughout the body. the differences between the parasympathetic and sympathetic nervous systems are summarized, mainly being that they produce different results in the organs that they innervate (stimulation vs. relaxation), originate in different areas of the spinal cord, and also have ganglia in different locations (autonomic ganglia or adrenal medulla for sympathetic and closer to the organs for parasympathetic).
the third section introduces the different types of ANS neurotransmitters that are dealt with in this lecture, with the two broad categories being cholinergic and catecholamine. the main cholinergic neurotransmitter is acetylcholine and it is associated with nicotinic and muscarinic receptors, which are differentiated by their location; neurons / skeletal muscle for nicotinic, and body tissue / CNS neurons for muscarinic. the other broad category of neurotransmitter is catecholamines, which include dopamine, norepinephrine, and epinephrine. a later slide describes the chain of synthesis of these three NT's from tyrosine: tyrosine to L-dopa to dopamine to norepinephrine to epinephrine.
nicotinic receptors are looked at in greater detail, first starting with the phenomenon of excitatory post synaptic potential's, also called end-plate potentials in these neuromuscular junctions between the post synaptic neuron and the skeletal muscle cell. this is caused when the release of acetyl choline causes an increase in the permeability of the ionotropic Na+ and K+ channels, causing a net influx of positive ions and therefore a depolarization of the membrane. the location is on the dendrite, and an example includes that of glucose.
muscarinic receptors, on the other hand, are not covered in much detail in terms of their physiology. they are found in the parasympathetic postganglionic synapses and associated with acetylcholine. two examples are given of muscarinic receptor action: the vagus nerve innervating the heart's SA node, the pacemaker, and hyperpolarizing the membrane by opening the K+ channels directly. the other example is stimulating smooth muscle contraction via IP3.
the next few slides deal with norepinephrine and epinephrine and their receptors, alpha and beta. not much physiology is covered here either, except to say that alpha receptors regulate Ca++ and K+ channels and beta receptors regulate smooth muscle, cardiac, and metabolism. beta 1 and 2 are also responsive to drugs, such as ephedra (Ma Huang), Propranolol, and amphetamines (ie: cocaine).
neuropeptides are then introduced as a different type of neurotransmittter, one that is synthesized and packaged into larger vescicles in the cell body, transported to the axon, and are released only with higher frequency stimulation (translating into higher concentration gradients of intracellular calcium), at which point they are co-released with other neuropeptides and create a longer lasting effect than neurotransmitters. neuropeptides act at much lower concentrations than neuotransmitters.
the last two slides are a huge chart of the entire peripheral nervous system, showing the somatic, parasympathetic and sympathetic divisions, the neurotransmitters secreted and receptors used in each synapse, and the end target of innervation. the somatic nervous system shows a single axon (motorneuron) going to the skeletal muscle, releasing ACh into the neuromuscular junction (NMJ) and picked up by a nicotinic receptor. the sympathetic nervous system shows one preganglionic cell synapsing in the autonomic ganglia with ACh and nicotinic receptors, with one of the post ganglionic branches going to smooth muscle, using norepinephrine and alpha/beta receptors, and the other branch going to the sweat glands with a muscarinic receptor and ACh neurotransmitter. the adrenal medulla is also part of the sympathetic, being innervated using ACh and releasing hormones (mainly epinephrine) directly into the bloodstream. the last branch is the parasympathetic, which uses muscarinic receptors and acetyl choline and goes to smooth muscle, cardiac muscle, and glands.
some larger thoughts about this chart: ACh and nicotinic receptors are always used in the synapses between pre and postganglionic neurons. alpha and beta receptors are only used in the sympathetic nervous system for smooth muscle and glands. muscarinic receptors are only used in the parasympathetic postganglionic synapses and the sweat glands of the sympathetic.
the second section gives an overview of the nervous system, specifically the peripheral nervous system and the distribution of neurons throughout the body. the differences between the parasympathetic and sympathetic nervous systems are summarized, mainly being that they produce different results in the organs that they innervate (stimulation vs. relaxation), originate in different areas of the spinal cord, and also have ganglia in different locations (autonomic ganglia or adrenal medulla for sympathetic and closer to the organs for parasympathetic).
the third section introduces the different types of ANS neurotransmitters that are dealt with in this lecture, with the two broad categories being cholinergic and catecholamine. the main cholinergic neurotransmitter is acetylcholine and it is associated with nicotinic and muscarinic receptors, which are differentiated by their location; neurons / skeletal muscle for nicotinic, and body tissue / CNS neurons for muscarinic. the other broad category of neurotransmitter is catecholamines, which include dopamine, norepinephrine, and epinephrine. a later slide describes the chain of synthesis of these three NT's from tyrosine: tyrosine to L-dopa to dopamine to norepinephrine to epinephrine.
nicotinic receptors are looked at in greater detail, first starting with the phenomenon of excitatory post synaptic potential's, also called end-plate potentials in these neuromuscular junctions between the post synaptic neuron and the skeletal muscle cell. this is caused when the release of acetyl choline causes an increase in the permeability of the ionotropic Na+ and K+ channels, causing a net influx of positive ions and therefore a depolarization of the membrane. the location is on the dendrite, and an example includes that of glucose.
muscarinic receptors, on the other hand, are not covered in much detail in terms of their physiology. they are found in the parasympathetic postganglionic synapses and associated with acetylcholine. two examples are given of muscarinic receptor action: the vagus nerve innervating the heart's SA node, the pacemaker, and hyperpolarizing the membrane by opening the K+ channels directly. the other example is stimulating smooth muscle contraction via IP3.
the next few slides deal with norepinephrine and epinephrine and their receptors, alpha and beta. not much physiology is covered here either, except to say that alpha receptors regulate Ca++ and K+ channels and beta receptors regulate smooth muscle, cardiac, and metabolism. beta 1 and 2 are also responsive to drugs, such as ephedra (Ma Huang), Propranolol, and amphetamines (ie: cocaine).
neuropeptides are then introduced as a different type of neurotransmittter, one that is synthesized and packaged into larger vescicles in the cell body, transported to the axon, and are released only with higher frequency stimulation (translating into higher concentration gradients of intracellular calcium), at which point they are co-released with other neuropeptides and create a longer lasting effect than neurotransmitters. neuropeptides act at much lower concentrations than neuotransmitters.
the last two slides are a huge chart of the entire peripheral nervous system, showing the somatic, parasympathetic and sympathetic divisions, the neurotransmitters secreted and receptors used in each synapse, and the end target of innervation. the somatic nervous system shows a single axon (motorneuron) going to the skeletal muscle, releasing ACh into the neuromuscular junction (NMJ) and picked up by a nicotinic receptor. the sympathetic nervous system shows one preganglionic cell synapsing in the autonomic ganglia with ACh and nicotinic receptors, with one of the post ganglionic branches going to smooth muscle, using norepinephrine and alpha/beta receptors, and the other branch going to the sweat glands with a muscarinic receptor and ACh neurotransmitter. the adrenal medulla is also part of the sympathetic, being innervated using ACh and releasing hormones (mainly epinephrine) directly into the bloodstream. the last branch is the parasympathetic, which uses muscarinic receptors and acetyl choline and goes to smooth muscle, cardiac muscle, and glands.
some larger thoughts about this chart: ACh and nicotinic receptors are always used in the synapses between pre and postganglionic neurons. alpha and beta receptors are only used in the sympathetic nervous system for smooth muscle and glands. muscarinic receptors are only used in the parasympathetic postganglionic synapses and the sweat glands of the sympathetic.
10.13.08 organ systems: metabotropic transmission
here's the first summary that i tried this semester:
this lecture introduces the concept of metabotropic transmission, which is essentially when membrane receptor proteins set off chains of reactions of proteins and enzymes which then mediate a cell response which is generally longer lasting, more amplified than that of ionotropic receptors. g proteins are the single most important transducer molecule in that they are the first intermediate which set off the chain reactions. they are energized by GTP and can affect ion channel permeability, create second messengers, and regulate protein transcription.
second messengers are then detailed, with an emphasis on cAMP, its synthesis and its actions. cAMP is synthesized when g proteins stimulate adenyl cyclate to make cAMP from ATP. the total cAMP in the cell is a summation of the stimulatory and inhibitory activity of g-proteins. cAMP then stimulates enzyme protein kinases, which then can have a plethora of effects on the cell. specific examples: affect excitability of cell by affecting permeability of non gated K+ channels. convert glycogen to glucose in the liver. release fatty acids from adipose cells. etc. etc.
the other two second messengers talked about in this lecture are IP3 and DAG. the synthesis pathway is: g proteins stimulate PLC to cleave PIP into IP3 and DAG. IP3 is responsible for Ca+ release in smooth muscle cells and DAG is responsible for cell growth and proliferation.
the last main concept in this lecture is the regulation of gene transcription and ion channel permeability (up and down regulation) by g-proteins. the former is accomplished by protein kinases stimulating CREB, which is a translational activator. the latter is accomplished by cAMP stimulating protein kinases to interact with transcription factors which then produce proteins that interact with the protein channels on a long term basis (contrast this with the way that g proteins sometimes directly bind to ion channels)
this lecture introduces the concept of metabotropic transmission, which is essentially when membrane receptor proteins set off chains of reactions of proteins and enzymes which then mediate a cell response which is generally longer lasting, more amplified than that of ionotropic receptors. g proteins are the single most important transducer molecule in that they are the first intermediate which set off the chain reactions. they are energized by GTP and can affect ion channel permeability, create second messengers, and regulate protein transcription.
second messengers are then detailed, with an emphasis on cAMP, its synthesis and its actions. cAMP is synthesized when g proteins stimulate adenyl cyclate to make cAMP from ATP. the total cAMP in the cell is a summation of the stimulatory and inhibitory activity of g-proteins. cAMP then stimulates enzyme protein kinases, which then can have a plethora of effects on the cell. specific examples: affect excitability of cell by affecting permeability of non gated K+ channels. convert glycogen to glucose in the liver. release fatty acids from adipose cells. etc. etc.
the other two second messengers talked about in this lecture are IP3 and DAG. the synthesis pathway is: g proteins stimulate PLC to cleave PIP into IP3 and DAG. IP3 is responsible for Ca+ release in smooth muscle cells and DAG is responsible for cell growth and proliferation.
the last main concept in this lecture is the regulation of gene transcription and ion channel permeability (up and down regulation) by g-proteins. the former is accomplished by protein kinases stimulating CREB, which is a translational activator. the latter is accomplished by cAMP stimulating protein kinases to interact with transcription factors which then produce proteins that interact with the protein channels on a long term basis (contrast this with the way that g proteins sometimes directly bind to ion channels)
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