BIO3303 Nervous System 3.pdf

Control Systems I : Nervous System Objectives (3 of 3) By the end of this lecture, you should know: How the ANS is regulated Neurotransmitters and receptors – types, how neurotransmitters are released and recognized Acetylcholine, epinephrine and norepinephrine Autonomic Nervous System (ANS) How is...

Control Systems I : Nervous System Objectives (3 of 3) By the end of this lecture, you should know: How the ANS is regulated Neurotransmitters and receptors – types, how neurotransmitters are released and recognized Acetylcholine, epinephrine and norepinephrine Autonomic Nervous System (ANS) How is it regulated? Fig. 7.16 Regulation of ANS by brain Fig. 7.21/8.22 Regulation of ANS by brain The hypothalamus plays a dominant role initiates fight-or-flight response regulatory centers for body temperature, food intake, and water balance. Medulla oblongata Contains centres involved in the regulation of breathing, heart rate, and BP Fig. 7.21/8.22 Autonomic reflex arcs Ex: Blood pressure Regulated by opposing action of sympathetic and parasympathetic branches Cardiovascular control center influences activity of ANS Cause adjustments in heart rate, stroke volume and vasoconstriction Blood pressure returns to normal PNS CNS PNS Fig. 7.22/8.23 Neurotransmitters Criteria to be classified as neurotransmitter: 1. Synthesized in neurons 2. Released at presynaptic membrane following depolarization 3. Bind to a postsynaptic receptor and cause a detectable effect Effect depends on the type of receptor – specific neurotransmitters bind to specific receptor types Fig. 4.26 5 Classes: Amino acids Biogenic amines Neuropeptides Acetylcholine ‘Other’ Spotlight: Ach, E, NE Ach – acetylcholine; cholinergic receptors (muscarinic and nicotinic) Biogenic amines E and NE – epinephrine and norepinephrine; adrenergic receptors (alpha and beta) Neurotransmitters Neurotransmitters Cholinergic Synapse (ACh): ACh synthesis exocytosis Fig. 4.17/5.22 Cholinergic Synapse: ACh release Fig. 4.16/5.21 Rate of APs arriving at axon terminal determines amount of neurotransmitter release Neuromuscular Junction 1. Action potential results in ACh release VG Ca2+ channels open and increase [Ca2+] leading to vesicle docking 2. Binds nicotinic ACh receptor (nAChR) on skeletal muscle nAChRs are ligand gated ion channels Ions (mostly Na+) depolarize muscle 3. Induces muscle contraction 4. AChE breaks down ACh into choline and acetate, terminating the signal. 5. Presynaptic cell takes up and recycles choline and acetate diffuses out of synapse. Skeletal muscle Fig. 4.16 and 4.17 Cholinergic Synapse (ACh) Nicotinic AChR NMJ, ganglionic synapses Ligand-gated, Ionotropic, rapid Effects are always excitatory (graded EPSP)(excitatory post-synaptic potential) Muscarinic AChR Postganglionic parasympathetic synapses Metabotropic, slow Diverse effects Excitatory or inhibitory (graded EPSP or IPSP) (inhibitory post-synaptic potential) Fig. 5.34 Nicotinic AChR (nAChR) Ligand-gated ionotropic receptor Excitatory effects ACh bind ligand binding-sites → conformational change Allows Na+ flow through (K+ also but driving force of Na+ influx is higher) Depolarize membrane (effector cell) → Graded excitatory post synaptic potential (graded EPSP) Fig. 12.16, Hill et. al. 2004 Nicotinic AChR Five subunits surround pore A variety of combinations of five different subunits α, β, γ, δ, ε, Each with several isoforms Different combinations, different properties Brain: mostly α4 and β2 ANS: α3, α5, α7, β2, β4 Fig. 4.29 Muscarinic AChR (mAChR) Metabotropic receptor Ligand (ACh) binds receptor and conformational change activates G-protein – G-protein coupled receptor G-protein: heterotrimer activated by GTP binding to αsubunit, α-subunit and βγ-complex interact to activate ion channels Leads to opening of ion channels and other intracellular events – signaling cascade Fig. 12.20, Hill et. al. 2004 Cholinergic Receptors Table 5.5 Adrenergic Receptors (ARs) Sympathetic synapses at effector tissue Respond to norepinephrine (NE) or epinephrine (E) released from sympathetic postganglionic neuron Different receptor types and subtypes Tissue specific distribution α adrenoreceptors (α1, α 2 ARs) β adrenoreceptors (β 1, β 2 ARs and more) Fig. 7.19/8.20 α1 Adrenergic Receptors sensitivity NE > E α1 ARs: NE binds → phosphorylates VG Ca2+ channels via PLC and PKC → opens inactivation gate Is involved in contraction of smooth muscles (except intestinal) e.g. vasoconstriction Fig. 4.31a/5.37a α2 Adrenergic Receptors Sensitivity NE > E α2 ARs: NE binds → dephosphorlylates VG Ca2+ channels via inactivation of AC, ↓[cAMP], inactivation of PKA (inactivation gate closed) Located on membrane of adrenergic axon terminals → inhibit release of NE Fig. 4.31b/5.37b β Adrenergic Receptors β ARs: NE binds → activates VG Ca2+ channels via AC, ↑ [cAMP] β 1 ARs (NE = E): primarily in heart ↑ heart rate and strength of contraction β 2 ARs (E > NE): prevalent in bronchioles of lungs bronchodilation (smooth muscles relax) Fig. 4.31c/5.37c Adrenergic Receptors Same neurotransmitter can have different effects depending on the type of receptor that is on the effector cell. smooth muscles contract smooth muscles relax Agonist vs Antagonist Agonist Agonist: a substance that binds to a receptor and initiates a signalling event (may include both the natural endogenous ligand as well as pharmaceutical agents that mimic the natural substance). signal Antagonist Antagonist: a substance that binds to a receptor but does not stimulate a signaling event. Interfere with the binding of the natural ligand. Also see Fig. 3.11/4.12 No signal Agonists and Antagonists Nicotinic AChR (SNS, PSNS) Agonist: nicotine → variable effects: both a stimulant and a relaxant Antagonist: curare → paralysis bungarotoxin → paralysis, suppression of breathing Curare darts Muscarinic AChR (PSNS) Agonist: muscarine → bronchoconstriction, bradycardia Antagonist: atropine → ↑HR Bungarus snake Amanita muscaria Agonists and Antagonists Adrenergic Receptors (SNS) Agonist: isoproterenol (non-specific) → treatment of bradycardia (slow heart rate) β2: salbutamol → treatment of asthma (bronchiole dilation) Antagonists: α: phentolamine, phenoxybenzamine → treatment of hypertension β: propranolol, sotalol → treatment of anxiety, cardiac arrhythmias Ventolin Evolution of the Autonomic NS Divisions of ANS often not as well defined in ‘lower’ vertebrates Greater reliance on circulating catecholamines (NE, E made by adrenal medulla, not a neuron) e.g. Dogfish: no sympathetic innervation of heart, relies completely on circulating catecholamines Exception in SNS – Adrenal medulla Preganglionic neuron synapses onto chromaffin cells (modified postganglionic neurons) of the adrenal medulla (highly modified sympathetic ganglion). Chromaffin cells (neurosecretory cells) secrete epinephrine and norepinephrine into circulation → widespread effects ACh Sympathetic Fig. 7.20/8.21 Evolution of the Adrenal Gland Fig. 3.38/4.41 Nervous system wrap up Information transmission in the nervous system relies on both electrical (AP) and chemical (synapses) events. The functional unit of the nervous system is a reflex arc; it is based on neurons, the structural unit of the nervous system. Nervous system complexity is achieved by structural and functional complexity (more neurons, more complicated interactions) The vertebrate NS consists of the CNS (brain and spinal cord) and PNS (afferent nerves, efferent motor nerves of the somatic and autonomic divisions). The CNS collects and integrates sensory input and determines appropriate motor output. Somatic motor neurons are specialized for fast transmission and are always excitatory. The ANS is a key system for the neural control of bodily function. It consists of two divisions differing in anatomy, pharmacology and physiology.