Session 7.5: intracellular signalling pathways 2 Flashcards
how does cardiac ventricular contractility occur
depolarisation -> sensed by voltage operated calcium channel -> allows calcium to enter -> activates ryanodine receptor -> contraction -> movement of calcium into SR through SERCA
magnitude of calcium entry trigger by depolarisation = change in calcium = magnitude of contraction
what can increase the inotropy in the heart
blood borne adrenaline and sympathetically released noradrenaline can interact with ventricular beta 1-adrenoreceptors to increase force (positive inotropy). the protein kinase A formed from signalling pathway can phosphorylate VOCC, allowing more calcium to enter next time the membrane is depolarised = contractility increases
how can smooth muscle be regulated
sympathetically released noradrenaline and blood borne adrenaline can interact with vascular smooth muscle alpha 1 -adrenoceptors to cause vasoconstriction
parasympathetically released acetylcholine acts on M3-muscarinic receptors to cause bronchoconstriction in bronchiolar smooth muscle
also can interact GI and genito-utinary smooth muscle
what do smooth muscle regulation all utilise
Gq-phospholipase C -IP3/Ca2+, DAG/protein kinase C pathways to pump calcium into cell, so increase PKC activity and larger contractility of smooth muscle
how is neurotransmitter release regulated
need large enough calcium to move vesicles so…
depolarisation of nerve -> Pq voltage gated calcium channels activated -> calcium influx -> synaptic vesicle fusion -> neurotransmitter release
note: GPCR near VOCCs so able to regulate channel activity
how is neurotransmitter release modulated
in CNS and periphery, by presynaptic G protein coupled receptors
morphine binds to u-opioid receptor, GDP-> GTP, GTP-alpha I subunit + gamma/beta -> the gamma/beta subunits bind to VOCC, less calcium enters and less neurotransmitter released (inhibits)
what are some key feature of GPCR
DIVERSITY
SPECIFICITY
AMPLIFICATION
