Membrane Excitability

What makes up outer leaflet

PC, SM, Glycolipids

What makes up inner leaflet

PE, PI, PS

Enzyme that makes phospholipids go from inner leaflet to outer leaflet

Lipid fippase

Enzyme that makes phospholipids go from outer leaflet to inner

Lipid Floppase

Extracellular Anchoring of Membrane Proteins

Glycosylphosphotidylinositol, N-linked glycosilation

Intercellular Anchoring of Membrane Proteins

N-terminal myrisotlyation,s-acetylation, s-palmtoylation

Remove Calcium from cells

SERCA, NCX, PMCA (plasma membrane calcium ATPase)

Calcium influx in cells

Ryanodine Receptors

IP3 Receptors

Store- Operated Calcium Channels

Voltage/Ligand Gated

Acid Extruders

NHE and NBC

Acid Loaders

CBE, CHE

Two types of Nav Channel

TTX-s and TTX-r

TTX-R residues

Polar

TTX-S residues

aromatic

S1-S3 in receptors

Gating Charging Transfer Centre

S4 in receptors

Voltage sensor

N-terminal in voltage gated receptors

Inactivation particle

Pore forming region of voltage gated receptors

S5-P-S6

Local Anaesthetics on Nav channels

Bind to S6 domains of pseudounit 1,2 and 4

Intercellular loop connecting pseudounit 3 and 4- inactivation particle

Gabapentenoids on Cav channels

Bind to alpha2delta subunit- stop channel being expressed on surface

Drugs that bind to L-type Cav channels

DHPs, phenylakalmines, benzothezepines

Drug that binds to N-type Cav channel

Ziconotide- chronic pain drug

Where does B subunit bind in Cav channels

Intercellular loop that connects s1 and s2

Cav Family 2

N,R,P/Q- neurotransmitter release

Cav family three

T type- cell excitabilty

4 types of K channel

Delayed Rectifiers

Transient A type Currents

Ca Activated

Inward- Rectifiers

types of Ca activated K channels

Large conductance (BK)

Small and Intermediate Conductance

How do BKs respond to Ca

Extra transmembrane domain (0)

How do Small and Intermediate calcium activated K channels sense Calcium

Bind via calmodulin

Example of BK channel

Kca 1.1

Sodium channel implicated in epilepsy

1.1, 1.2

Sodium channel implicated in arrythmia

1.5

Sodium channel implicated in pain

1.7

Fast inactivation of voltage gated channel

N type

Slow inactivation of voltage gated channel

C- type

Example of depolarising neuromuscular inhibitor

Suxamethonium

Example of non-depolarising neuromuscular inhibitor

Atracurium, Vecuronium

Drug used to help nicotine addiction

Varenicline

Drug for alzheimer’s that directly acts on nAChR

Galatamine

Drug that acts on snare proteins

Botulinium

Drugs that act at acetylcholinesterase to treat Myasthenia gravis

neostigmine, pyriostigmine

Lambert Eaton Myasthenic Syndrome

Autoantibodies for presynaptic Cav channels

Acetylcholinesterase inhibitor that used to treat alzheimers

Rivastigmine

Drug for treatment of Lambert Eaton Mysasthenic Syndrome

b-4 diaminopyridine

Treatment for sarin

Atropine, Pralidoximine

Slow channel MS mutations

AlphaV249F

AlphaG153S

AlphaV249F

2nd transmembrane domains- close to leucine residues

Increased opening rate

AlphaG153S

3+4 loop- ACh binding site- slow closing

Drugs to treat slow channel myasthenic syndromes

Quinidine, Fluoxetine

Mutation in Fast Channel CMS

Epsilon- P121L

Decreased response to ACh

Cause of slow depolarisation- in AV

Cav 1.2

Cause of rapid repolarisation in ACN

Cav 3.1

What causes the funny current

HCN- activated at hyperpolarisation

Domain on HCN

CNBD

Medication that blocks HCNs

Ivabradine

Cause of steep incline in Ventricular Myocyte

Nav 1.5

Cause of decline in ventricular myocytes

Kv 4.2/4.3

Cause of flattening on Vm in myocytes

L type calcium channel

Delayed K+ rectifier Kv 7.1

Steep decline in myocytes

More K+ channels and hERG

hERG

K channel active when membrane potential is less then 0

What does hERG define?

QT

What takes up glucose in insulin B cells

GLUT2

What makes up ATP sensitive K channels

Kir 6.2, Sur

Barriers in the CNS

Blood Brain interface

Blood CSF interface

CSF blood interface

What connects cerebral endothelium

tight junctions and adherins

What gives cerebral endothelium high electrically resitance

Actin cytoskeleton

Where is the blood Brain interface

Cerebral endothelium

Where is the Blood- CSF interface

epithelial cells of choroid plexus

Where is the CSF- blood barrier

vascular arachnoid epithelium

What does lateral segregation form

Neurodomains

Protein involved in neurodomains

Caveolin- forms caveolae

Where is BBB not present in brain

Circumventricular organs- fenestrated cerebral endothelium

Drug to treat parasitic worms

Ivamectin

What breaks up Ivamectin

p-glycoprotein

Vesicle associated proteins

Synaptobrevins and Synaptotagmins

Membrane Associated vesicle proteins

SNAP25 and Syntaxins

Zippering

Formation of SNARE pins

Ca2+ sensory in vesicles

syntaptotagmin

What does syntaptotagmin do in presence of Calcium

Binds to phospholipids

What causes SNARE pins to dissociate

NSF

Protein for vesicle recycling

Clathyrn- protein lattice

Facillitation mechanisms

Residual Calcium build up, Iontropic autoreceptor activation

Depression Mechanisms

Vesicle Depletion

Metabotropic Autoreceptor Activation

Ionotropic Receptor Desensitisation

Reduced in vesicle depletion

Readily Reusable Pool

Probablility

Mean No of vesicles involved in release/ number of active sites

Single Channel Current

Single Channel Conductance x Driving Force (Vm- Erev)

Total Macroscopic Current

N x F0 x sum of microscopic currents

Conductance

Current over Voltage (Voltage= Vm-Erev)