Lecture_5-Calcium_signaling

Ca2 occurs typically upon receptor activation by

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Ca2+ occurs typically upon receptor activation by: neurotransmitters, hormones or growth factors or by activation of voltage-gated Ca2+ channels (VGCCs) IP3 receptors on ER control the majority of Ca2+ I release –P LC IP3 stimulates IP3 receptors on ER rise in Ca2+ – Sequestered Ca2+ in the ER lumen can sensitize the receptor to IP3 (facilitating subsequent release) – Low cytoplasmic Ca2+ also sensitize the receptor (feed-forward mechanism), while higher Ca2+ inhibit it (negative-feedback mechanism) Ryanodine receptors on ER – Also a homotetramer like the IP3 receptor and has structural homology with the IP3 receptor – Mostly in skeletal muscle – Ca2+ is the ligand for the receptor and thus, the receptor is considered a “Calcium-induced Calcium Release” ( CICR ) receptor (IP3 receptor always requires IP3) – Can also be activated by cAPDr (cyclic adenosine diphosphate ribose), which increases the probability of receptor opening in response to Ca2+
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Ca2+ signaling sources VGCCs found in a variety of excitable cell types including neurons – Activated by membrane depolarization (by action potential or opening of ligand- gated ion channels) and inhibited via negative feedback by rises in Ca2+ I – Work in a manner akin to the voltage-gated Na+ channels that contribute to the action potential – Key role in neurotransmitter release – 5 different VGCC subtypes that differ in their gating kinetics, modes of inactivation, Ca2+ regulation and sensitivity to toxins may serve different cellular functions • L, T, N, P, Q and R-types with T-types (pace-maker) being activated by low voltage and the others by high voltage • N-type (neuronal) are inactivated more rapidly than the others and are the major VGCCs involved in neurotransmitter release (inhibited by conotoxin GVIA) LGCCs Ionotropic Ca2+ channels that are gated by binding of an agonist; some provide sufficient Ca2+ entry to induce signaling cascades Typically non-specific cation channels Classic example is the NMDA subtype of iGluR
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Ca2 occurs typically upon receptor activation by...

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