Results for "Ca2 "

Lecture 06: Ca Signalling and Disease -> Cytotoxic Ca2+ Overload

Lecture 04: Ca2+ Signalling in Health and Disease

Lecture 03: Ca2+ Signalling and Disease

L20 Ca2+ signal dysfunction in disease

L19 Decoding Ca2+ Signals

L17 The Phosphoinositide Signalling Pathway and Ca2+ functions and mechanisms

N371: Ca2+ imaging

Regulation of Ca2+ and Phosphate (Sayner)

pt 4: Adrenal gland structure Cortex (steroids) + medulla (catecholamines) Three adrenal cortex layers Zona glomerulosa, fasciculata, reticularis Zona glomerulosa Secretes aldosterone (mineralocorticoid) Aldosterone function Increases Na+ reabsorption, K+ excretion; raises blood pressure Aldosterone release triggered by Low BP, high K+, renin-angiotensin system, ACTH Renin-angiotensin system Low BP → renin → Ang I → Ang II → aldosterone + vasoconstriction Zona fasciculata Secretes cortisol (glucocorticoid) Cortisol function Increases glucose, suppresses immune system, maintains blood pressure High cortisol effects Immune suppression, muscle wasting, hyperglycemia Zona reticularis Secretes adrenal androgens Adrenal androgens Weak sex hormones contributing to puberty and libido Adrenal medulla hormones Epinephrine and norepinephrine Epinephrine effects Increases heart rate, metabolic rate Norepinephrine effects Increases vasoconstriction and blood pressure Pancreas function Exocrine (digestive enzymes) + endocrine (insulin, glucagon) Alpha cells in pancreas Produce glucagon Beta cells in pancreas Produce insulin Glucagon function Increases blood glucose via glycogenolysis and gluconeogenesis Insulin function Decreases blood glucose by increasing cellular uptake Somatostatin from pancreas Inhibits insulin and glucagon release Type 1 diabetes Autoimmune destruction of beta cells → no insulin Type 2 diabetes Insulin resistance; cells do not respond to insulin Effects of insulin Promotes glucose uptake, fat storage, glycogen formation Ovarian hormones Estrogen and progesterone Estrogen function Female development, menstrual cycle regulation Progesterone function Maintains uterus for pregnancy Testicular hormone Testosterone Testosterone functions Male traits, sperm production, libido Placental hormones hCG, estrogen, progesterone hCG function Maintains corpus luteum early in pregnancy Kidney hormone EPO (erythropoietin) EPO function Stimulates RBC production when oxygen is low Heart hormone ANP (atrial natriuretic peptide) ANP function Decreases blood pressure by reducing blood volume GI hormones Gastrin, secretin, CCK regulate digestion Skin hormone precursor Produces vitamin D precursor (cholecalciferol) Adipose hormone Leptin Leptin function Signals satiety and regulates metabolism Cushing’s syndrome Excess cortisol → moon face, buffalo hump, high glucose Addison’s disease Low cortisol/aldosterone → fatigue, low BP, hyperpigmentation Pheochromocytoma Adrenal medulla tumor causing excess epinephrine Conn’s syndrome Excess aldosterone → high BP, low K+ Hyperthyroidism symptoms Weight loss, heat intolerance, anxiety, fast heartbeat Hypothyroidism symptoms Fatigue, weight gain, cold intolerance Goiter Enlarged thyroid due to iodine deficiency or overstimulation Primary endocrine disorder Problem in the gland itself Secondary endocrine disorder Problem in pituitary or hypothalamus Calcitriol (active vitamin D) Increases Ca2+ absorption in intestines Endocrine disruptors Chemicals interfering with hormone actions

pt 4: Adrenal gland structure Cortex (steroids) + medulla (catecholamines) Three adrenal cortex layers Zona glomerulosa, fasciculata, reticularis Zona glomerulosa Secretes aldosterone (mineralocorticoid) Aldosterone function Increases Na+ reabsorption, K+ excretion; raises blood pressure Aldosterone release triggered by Low BP, high K+, renin-angiotensin system, ACTH Renin-angiotensin system Low BP → renin → Ang I → Ang II → aldosterone + vasoconstriction Zona fasciculata Secretes cortisol (glucocorticoid) Cortisol function Increases glucose, suppresses immune system, maintains blood pressure High cortisol effects Immune suppression, muscle wasting, hyperglycemia Zona reticularis Secretes adrenal androgens Adrenal androgens Weak sex hormones contributing to puberty and libido Adrenal medulla hormones Epinephrine and norepinephrine Epinephrine effects Increases heart rate, metabolic rate Norepinephrine effects Increases vasoconstriction and blood pressure Pancreas function Exocrine (digestive enzymes) + endocrine (insulin, glucagon) Alpha cells in pancreas Produce glucagon Beta cells in pancreas Produce insulin Glucagon function Increases blood glucose via glycogenolysis and gluconeogenesis Insulin function Decreases blood glucose by increasing cellular uptake Somatostatin from pancreas Inhibits insulin and glucagon release Type 1 diabetes Autoimmune destruction of beta cells → no insulin Type 2 diabetes Insulin resistance; cells do not respond to insulin Effects of insulin Promotes glucose uptake, fat storage, glycogen formation Ovarian hormones Estrogen and progesterone Estrogen function Female development, menstrual cycle regulation Progesterone function Maintains uterus for pregnancy Testicular hormone Testosterone Testosterone functions Male traits, sperm production, libido Placental hormones hCG, estrogen, progesterone hCG function Maintains corpus luteum early in pregnancy Kidney hormone EPO (erythropoietin) EPO function Stimulates RBC production when oxygen is low Heart hormone ANP (atrial natriuretic peptide) ANP function Decreases blood pressure by reducing blood volume GI hormones Gastrin, secretin, CCK regulate digestion Skin hormone precursor Produces vitamin D precursor (cholecalciferol) Adipose hormone Leptin Leptin function Signals satiety and regulates metabolism Cushing’s syndrome Excess cortisol → moon face, buffalo hump, high glucose Addison’s disease Low cortisol/aldosterone → fatigue, low BP, hyperpigmentation Pheochromocytoma Adrenal medulla tumor causing excess epinephrine Conn’s syndrome Excess aldosterone → high BP, low K+ Hyperthyroidism symptoms Weight loss, heat intolerance, anxiety, fast heartbeat Hypothyroidism symptoms Fatigue, weight gain, cold intolerance Goiter Enlarged thyroid due to iodine deficiency or overstimulation Primary endocrine disorder Problem in the gland itself Secondary endocrine disorder Problem in pituitary or hypothalamus Calcitriol (active vitamin D) Increases Ca2+ absorption in intestines Endocrine disruptors Chemicals interfering with hormone actions

# Synaptic transmission and the vesicle cycle ILO: - the two fundamental synaptic mechanisms by which excitable cells and in particular neurones can affect one another's function: electrical or chemical synaptic communication - how a neurotransmitter supporting chemical synaptic communication is defined and the diversity of types of small molecules that can be defined as being a neurotransmitter - how these are stored in small membranous vesicles, what constitutes the classical vesicle cycle and full collapse vesicle fusion during release - the experimental evidence for this full collapse fusion release model and how the vesicle membrane is recycled - further experimental evidence for an alternative to this model: the "kiss and run" model of vesicle cycling - the proteins that make up the release machinery and how they are readied for release during "docking" and "priming" - what happens to these proteins during the release process and the subsequent retrieval of vesicle membrane following full collapse fusion # Types of synapse - **chemical synapse** - molecules stored in vesicles - molecules diffuse across a gap - relatively slow - unidirectional - majority of synaptic transmission in the nervous system - **electrical synapse** - holes in adjoining cell membranes - linked by channels - gap junctions or connexons - signalling is very fast - bidirectional - direct electrical coupling between cells - electrical synchronisation in the heart - relatively rare in the nervous system - inhibitory interneurons or local networks # Chemical synapse Key functional roles - Neural computation - integration of many input +/- - Exhibit plasticity - development, learning and memory - Act as targets for drug action - neurotransmitter synthesis, release, receptors, uptake, degradation to produce a broad range or complex series of effects - inc functional flexibility ## Neurotransmitter 6 criteria :  ### Types  - amino acids - amines - purines - peptides - **dales principle** - neurons release just one transmitter at all of its synapses - how is dales principle challenged? - challenged by co existence and co release of small molecule transmitter and peptides by interneurons eg GABA and enkephalins - and more than one small molecule transmitter in some projection pathways eg L glutamate and dopamine ## Vesicles - neurotransmitters are likely to be stored in one type of vesicle ### Types  For LDCVs - concentration is lower because of the relatively proximity to the voltage gated channels - only seen when there is sustained AP in a more global manner rather than restricted to synaptic active zone ### Cycling  1. vesicle is filled with neurotransmitter with appropriate transporter which uses ATP as an energy source to drive against conc gradient and fill the vesicle 2. vesicle collected in to reserve pool, mobilised to active zone for docking 1. atp dependent process 3. primed to be sensitive to calc conc to initiate membrane fusion 1. also atp dependent 4. exocytosis following inc in intracellular conc of calcium 5. vesicle membrane fully collapses into the membrane 6. loss of membrane recovered with endocytosis, calcium dependent with coated pits 1. uncoating requires atp 7. small vesicles become part of endosome, all recycled 8. then pinched off again to start the cycle ### Evidence for full fusion/collapse - slam freezing - rapidly cooling of the neuromuscular junction on a metal block after electrical stimulation of motor neurone axon fibres to initiate acetylcholine release - sections of the presynaptic membrane were visualised at different types after electrical stimulation to follow any changes in presynaptic membrane - activity led to increase in membrane surface area - therefore vesicle recycling ### Step 1 - docking - close association with plasma membrane - synaptic vesicles only dock at active zone - presynaptic area adjacent to signal transduction machinery - active zones differ between neurons by vesicle number ### Step 2 - priming - ready for release - maturation of synaptic vesicle - made competent to release transmitter - requires ATP - conformational change in proteins that drive release ### Step 3 fusion/exocytosis - full fusion of synaptic vesicle and presynaptic terminal membrane - requires calcium - calcium sensor protein - fusion induces exocytosis - takes 1ms ### Step 4 endocytosis - recovery of fused membrane - triggered by inc intracellular calcium - involves cytoskeletal protein lattice formation from clathrin monomers - this helps to pinch off membrane with clathrin coated pits - takes about 5 seconds - ATP dependent ### Step 5 - recycling - mechanism to conserve synaptic vesicle membrane via endosome - decoating of clathrin coated pits is also atp dependent - vesicles refill with transmitter - atp dependent ### Kiss and Run Model? - fast recycling and low capacity, favoured at low frequency stimulation - may be majority of glutamate release in hippocampus - whereas classical is slow, high capacity, favoured at high frequency stimulation - full vesicle fusion may not be required - neurotransmitter leaks out of small fusion pores - SSVs recycled intact - and not recycled as clathrin coated vesicles via the endosome Functional evidence - flickering capacitance changes instead of up stepping capacitance - capacitance dependent on surface area ### Targeting vesicles Vesicle associated proteins - synaptobrevins VAMP - synaptotagmins Plasma membrane associated proteins - SNAP-25 - syntaxins ### Snares for release - synaptobrevin - single transmembrane spanning - t snare - syntaxin - single transmembrane spanning - SNAP-25 - anchored to membrane by S-acylation ### Release machinery in the different steps     Syntaxin regulatory domain is important in maintaining a tight connection to the cell membrane Snares form a tighter complex during priming - atp dependent - Habc domains binding assisted by Munc18 - zippering - formation of the SNARE pins What is the Ca2+ sensor? - synaptotagmin - found on vesciles - binds to SNARE pins in absence of Ca2+ - during priming - binds to phospholipids in C region in presence of Ca2+ - Ca2+ binding may cause synaptotagmin to pull vesicle into membrane Why must SNAREs disassociate? - to allow internalisation of empty vesicles - re docking of another vesicle - involves NSF - ATPase which binds to the SNARE-pin complex to facilitate disassociation

Blokátory Ca2+ kanálů

[CA26-10] Week 16: SELF-STUDY

CA2: Voice disorders

Data Mining CA2

Lecture 9: Membrane Function - Regulation of pH and Ca2+

IP3 /Ca2+/Protein Kinase C pathway

NEUS 609 - Ramsey's Practice quiz

[CA26] September Progress Test

CA2