Cell signaling transduction mechanisms

Cell Signaling1. Synthesis, release, transport of signaling molecules

- neurotransmitters, hormones, etc- ligand binds to a specific receptor

2. Reception of information by target cells

3. Signal transduction- receptor converts extracellular signal into

intracellular signal- causes change in the cell

4. Response by the cell

Fig. 6-3, p. 137

Cell Signaling

Receptors

Figure 12.2b

Functional Overview of the Nervous System

Figure 13–14

5 Steps in a Neural Reflex

Nerve Structure

Neuron Structure

Electrochemical Gradients

Figure 12.12

Figure 12.11

An Introduction to the Resting Potential

Electric eel600 volts

Figure 12.13

*Canalopatías“channelopathies”

The first demonstration that channelopathies could affect nerves as well as muscles came in 1995, when researchers discovered that episodic ataxia type 1, a rare autosomal dominant disease, results from mutations in one of the potassium channel genes.

Paramyotonia congenita is due to mutations in the gene coding for the α1 subunit of the sodium channel,

Thomsen’s disease (autosomal dominant myotonia congenita) and Becker’s disease (autosomal recessive myotonia congenita) are allelic disorders associated with mutations in a gene coding for skeletal muscle chloride channel.

Familial hyperkalaemic periodic paralysis is due to mutations in the same sodium channel gene as that affected in paramyotonia congenita, while

Familial hypokalaemic periodic paralysis results from mutations in the gene coding for the α1 subunit of a skeletal muscle calcium channel.

Synaptic Transmission

Electrical synapses

Chemical synapses

Fig. 6-5, p. 139

Receptores:

Ionotróficos Metabotróficos

Neuropeptidos (encefalinas y endorfinas), endocannabinoides

(Glutamato)

(Tyrosina)

(Histidina) (Triptófano)

Fig. 40-10b, p. 858

Axon of presynaptic neuron

Synaptic terminal

Voltage-gated Ca2+ channel 1

Ca2+Synaptic vesicle2

Neuro- transmitter molecule

3

4

Ligand-gated channels

Postsynaptic membrane

5

Postsynaptic neuron

Receptor for neurotransmitter

How a neural impulse is transmitted across a synapse.

Ion Channel–Linked Receptor

Voltage-Activated Ion Channels

Tetradotoxina (pez globo), Saxitoxina (dinoflagelado marea roja) y cocaína –bloquean canales sodio voltajeCiguatoxina– facilitan canales sodio voltaje

Zombis– Tetradotoxina (bloquean canales sodio) + Datura (campana) –anticolinérgico.

*Canalopatías“channelopathies”

Figure 12.2b

Anatomy of a Multipolar Neuron

Figure 12.15

Depolarization and Hyperpolarization

EPSP – IPSP Interactions

Figure 12.23

Voltage-Activated Ion ChannelsDuring an Action Potential

Transmission of an Action

Potential

No-myelinadasTypeC 2mph

MyelinadasTypeB 40mphTypeC 268mph

Fig. 40-10b, p. 858

Axon of presynaptic neuron

Synaptic terminal

Voltage-gated Ca2+ channel 1

Ca2+Synaptic vesicle2

Neuro- transmitter molecule

3

4

Ligand-gated channels

Postsynaptic membrane

5

Postsynaptic neuron

Receptor for neurotransmitter

(b) How a neural impulse is transmitted across a synapse.

GABA y Serotonina

Receptor nicotínico Acetilcolina

Bungarotoxina (de la serpiente krait) antagonista receptor nicotínico AcetilcolinaParálisis y fallo respiratorio

Myasthenia gravis

Botulinum toxin Clostridium botulinum

Tetanus toxin & Strychnine

Fig. 6-3, p. 137

Fig. 6-5, p. 139

Receptores:

Ionotróficos Metabotróficos

Fig. 6-5, p. 139

G Protein–Linked Receptors

Fig. 43-13a, p. 933

1

2

5

34

Parasympathetic neuron

Acetylcholine

Acetylcholine receptor K + channel K +

Plasma membrane

G-protein

K +

Cardiac muscle

Receptor muscarínicopara acetilcolina

Fig. 43-13b, p. 933

Sympathetic neuron

1

Norepinephrine

-adrenergic receptor

Gate open

G protein Plasma membrane

2 6 Ca2+

Adenylyl cyclase

4ATP Ca2+

3

cAMP 5Cardiac muscle

Protein Kinase

Second Messenger

Signal Amplificationand SignalIntegration

Receptor Affinity-dissociation constant

Receptor Down Regulation-receptor mediated endocytosis-desenzitation

Drugs as agonist and antagonists

Isoprotenerol (asthma) / propanolol hypertension) (B-adrenergic receptor)

Famotidine (Pepcid AC) / Cimetidine (Tagamet)(histamine receptor)

cAMPAumenta fuerza contracción corazónRelajación músculos lisosSecresión de NaCl en epitelio intestinal

Inhibidores de fosfodiesterasa:cafeína y teofilina

Proteína Gs y Gi

Toxina del cólera (Gs)Inhiben hidrólisis de GTP

Toxina pertussis (Gi) (Tos ferina)Inhiben sustituir GTP por GDP

G Protein and cAMP

Fig. 43-13b, p. 933

Sympathetic neuron

1

Norepinephrine

-adrenergic receptor

Gate open

G protein Plasma membrane

2 6 Ca2+

Adenylyl cyclase

4ATP Ca2+

3

cAMP 5Cardiac muscle

Protein Kinase

Fig. 43-13a, p. 933

1

2

5

34

Parasympathetic neuron

Acetylcholine

Acetylcholine receptor K + channel K +

Plasma membrane

G-protein

K +

Cardiac muscle

Receptor muscarínicopara acetilcolina

Esteres de forbolMimetizan DAG

Second Messengers

Calcium Regulation

Sildenafil inhibeFosfodiesterasa de cGMP

Long-Term Potentiation (LTP)

Enzyme-Linked Receptors

EGF- cancer de seno, glioblastoma y fibrosarcoma

TGFβ- 30% cancer de ovario y cancer colorectal

Smad4- 50% cancer de páncreas

Smad4- 50% cancer de páncreas

The tumor suppressor gene Smad4 (DPC4) at chromosome 18q21.1 belongs to the Smad family, which mediates the TGFb signaling pathway suppressing epithelial cell growth.