Calcium Signalling. Why Calcium? [Ca 2+ ] i maintained very low – Prevents precipitation of organic anions.

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Presentation transcript:

Calcium Signalling

Why Calcium? [Ca 2+ ] i maintained very low – Prevents precipitation of organic anions

Why Calcium? Divalency - stronger protein binding than monovalent ions. Large [Ca 2+ ] gradient [10 -7 vs M]

PM Ca 2+ -ATPase ER Ca 2+ -ATPase – Calsequestrin Mitochondrial high capacity (low affinity) pump

Target TissueSignaling MoleculeMajor Responses LiverVasopressinGlycogen breakdown PancreasAChAmylase secretion Smooth muscleAChContraction Mast cellsAntigenHistamine secretion Blood plateletsThrombinaggregation

Turn the Pathway Off Voltage-gated Ca 2+ channels inactivate IP 3 rapidly dephosphorylated Ca 2+ rapidly pumped out Phosphatases are activated (CaMKII)

Ca 2+ as a 2 nd Messenger (cont’d) Ryanodine Receptors (RyR) Important for skeletal muscle Caffeine is an example of a reversible activator of RyRs IP3 receptors Inositol-1,4,5-P3

Gq Signalling - Calcium Signalling Tyrosine kinase Signalling – Calcium Signalling

Paari Dominic Swaminathan et al. Circulation Research. 2012;110: Copyright © American Heart Association, Inc. All rights reserved.

The domain structure of a calmodulin-dependent protein kinase II (CaMKII) monomer. Paari Dominic Swaminathan et al. Circulation Research. 2012;110: Copyright © American Heart Association, Inc. All rights reserved.

Ca-Responsive Transcriptional Activation cAMP-response element (CRE) CaM KII and Ras-ERK1/2 signaling pathways NFAT

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