This document discusses cell signaling pathways and second messengers, focusing on calcium signaling. It defines cell signaling and second messengers, noting that calcium ions serve as a ubiquitous second messenger. It describes the roles of calcium in various cellular processes and the mechanisms that regulate intracellular calcium levels, including calcium entry through voltage-gated and ligand-gated calcium channels, and calcium extrusion via sodium-calcium exchange. It further explains inositol 1,4,5-triphosphate (IP3) signaling, where IP3 binds to IP3 receptors on the endoplasmic reticulum to trigger the release of calcium stores into the cytosol.

1. Nitin Raosaheb Kale
M.Pharm 1st year
Faculty : Pharmacology
Presented By:
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2. CONTENT
1. Introduction
2. What is cell signaling pathway..?
3. What is second messenger..?
4. Calcium ion
5. Regulation of Intracellular Calcium Levels
6. Calcium entry mechanisms
7. Calcium Extursion mechanisms
8. Inositol 1,4,5- triphosphate (IP3)
9. What is the IP3 signaling pathway..?
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3.  Cell signaling is discovered by sir. Martin Rodbell in 1980.
 Cell to cell communication.
 The Ability of a cell to receive, process and transmit signals with its
environment and with itself.
Fig. 1.1
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4. WHAT IS SECOND MESSENGER..?
 Second messenger are molecules that relay signals from
receptors on the cell surface to target molecules Inside
the cell.
 Response – specific , amplified , tightly regulated and
coordinated.
 A series of signaling events that mediate the response to
each stimulus.
 Chemical and physical messengers interact with
receptors in the plasma membrane , cytoplasm or
nucleus.
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5. TYPES OF SECOND
MESSENGER
Fig. 1.2
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6. • Ca ion is important second messenger molecule.
• Ca ions serves as a ubiquitous second messenger in all eukaryotes
• Ca is a highly versatile intracellular signal capable of regulating many
different processes.
• Low cytoplasmic Ca at rest (10-100M)
• Our life start with unitary event of fertilization.
• In the heart beating there is Ca dynamics which generate action potential .
Fig. 1.3
2+
2+
2+
2+
2+
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7. Ca+2
Fertilization
Metabolism
Secretion
Neuronal
Activity
Cell Division
Cell Motility
Muscle
Contraction
Phagocytosis
Fig 1.4
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8. • Famous accident story of sidney ringers technician story
• Most of the Ca in a resting cell is sequestered in organells
ER & SR , Mitochondria.
Free Ca is kept to a low level about 10 .
• The Ca concentration in tissue fluid is about 2.4mM.
• Regulation of Ca involves three main mechanisms.
1. Control of Ca entry .
2. Control of Ca extrusion.
3. Exchange of Ca between the cytosol and the intracellular
stores.
2+
2+ -7M
2+
2+
2+
2+
2+
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9.  There are four main routes by which Ca enters cell
across the plasma membrane:
1.Voltage- gated Calcium Channels(VGC)
2. Ligand-gated Calcium Channels(LGC)
3. Store-operated Calcium Channels(SOCs)
4. Na - Ca exchange.
2+
2+
+
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10. Fig.1.5 : Regulation of intracellular calcium.
Plasma Membrane
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11. Calcium Extrusion Mechanisms
 The exchanger can function in reverse if
[Na ]I rises excessively, resulting in
increased Ca entry into the cell.
 The effect of digoxin on cardiac muscle
involves this mechanism.
+
2+
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12. Calcium Signaling Pathway
 Neurotransmitters, hormones, growth, factors or
chemical stimulation.
 Excitation of cell membrane.
 Intracellular Ca Increases
 Activation of Ca signaling pathway
2+
2+
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13. Process of Calcium Signaling Pathway
 There are two principal sources of Ca2+ for signaling
1. Ca2+ that enters the cell from outside cells use this sources
of signal Ca2+ by activating various entry channels.
a) Voltage –operated channels(VOCs)
b) Receptor-operated channels(ROCs)
c) Second-messenger-operated channel(SMOCs)
d) Store-operated Channels(SOCs)
2. Ca2+ signaling comes from internal Ca2+ store that is
primarily
located in the endoplasmic reticulum/ sarcoplasmic
reticulum(ER/SR)
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14. 14-21

15. Role of Ca in long term
potentiation
 LTP relies on calcium influx at NMDA glutamate receptors
 Calcium channels controlled by the NMDA receptor are blocked by a
magnesium ion
- Magnesium ion is ejected by:
1.Simultaneous glutamate binding AND .
2. Depolarization of the postsynaptic cell
(By activity at AMPA receptors on
the membrane)
2+
Fig 1.06
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16. Formation of bones and teeth
Calcium is a major structural element in bones and
teeth.
Bone is a dynamic tissue that is remodeled
throughout life due to osteoclasts and osteoblasts.
In bone calcium and phosphate combined together
in the crystalline complex:
Hydroxyapatite [Ca10(PO4)6(OH)2].
This complex provides the hard and rigid structure
of bone which is essential to its function.
Bone also acts as a store of calcium for other body
functions.
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17.  IP3 is hydrophilic in nature
 Agonist for internal calcium channel
 Ca2+ rises
 Multiple effect through Ca2 binding G-protein
 This soluble molecule diffuses through the cytosol
and binds to receptor on the ER causing the release
of calcium ions (Ca2+) into the cytosol.
Fig 1.07
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18. Fig 1.08
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19. I. GPCR After signal binding GPCR get active.
Trimer get monomer i.e. α, β, γ.
α- bound GTP.
PLC enzyme cleave to PIP2 into DAG & IP3
IP3 get attached to IP3 gated channel on ER.
Ca2+ level in cytosol
Ca2+ bounds with PKC
PKC ACTIVE
Target protein (+p)
Response
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20. Fig 1.13
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21. Thank you…!
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