Session 6 LT2 CHANGING MEMBRANE POTENTIAL

Question 1

WHAT IS THE CONNECTION BETWEEN CHANGING THE MEMBRANE POTENTIAL AND SIGNALLING?

Answer 1

• The changes in membrane potential underlie many forms of signalling in cells.
  Eg. Action potentials in nerve cells
• Triggering and controlling muscle contraction
• Control of secretion of hormones and neurotransmitters ( action potential insulin and synaptic cleft)
• ## Post synaptic actions of Fast synaptic transmitters

Question 2

Define Depolarisation

Answer 2

• DECREASE in the size of membrane potential from its normal value
• Cell interior becomes less negative ( more positive)
• eg from -70 mV to -50 mV

Question 3

DEFINE HYPERPOLARISATION

Answer 3

• INCREASE in the size of a membrane potential from its normal value.
  -Cell interior becomes more Negative
  Eg from -70 mV to -90 mV

Question 4

OPENING OF WHAT CHANNELS CAUSE DEPOLARISATION AND HYPERPOLARISATION?

Answer 4

Depolarisation - caused by Opening of Na+ and Ca2+
Hyperpolarisation - caused by Opening Cl- and K+ channels

Therefore changes in MP are caused by changes in activity of ION CHANNELS

Question 5

How long does an action potential last?

Answer 5

4-5 milli seconds

Question 6

What is the connection between membrane potentials and ion permeability?

Answer 6

• You have membrane potentials because of selective permeability
• Therefore changing the permeability of these ions will consequently change the MP
• Changes in membrane potential occur due to change in activity of IC
• Increasing the membrane permeability of a ion will mean MP will move towards the EP of that ion.

Question 7

Describe the relation ship between membrane permeability, EP and MP:

Answer 7

• MP - due to selective permeability
• increasing permeability to a particular ion means MP moves towards EP of that ion.
• Eg. At resting state the membrane is more permeable to k+ therefore MP closer to EK but not exactly the same because other channels are open.

Question 8

WHAT DO WE MEAN WHEN WE SAY REAL MEMBRANES HAVE IMPERFECT SELECTIVITY?

Answer 8

• Real cell membranes are not permeable to just one Ione they have channels open for more than one type of ion
• Therefore the contribution of each ion to membrane potential will be dependent on the permeability of ion. (= conductance) dep no channels open- GHK equation the permeability coefficient for ion moving in likely to be different to moving out - basis of Nernst eq

Question 9

Explain conductance

Answer 9

• Real cell membranes more than one ion channel open therefore the contribution each ion plays on the MP depends on permeability of the ion
• Depends on the number of channels open.
• Resting state membrane more perm to K+ therefore MP closer to EK

Question 10

GIVE AN EXAMPLE OF LESS SELECTIVE RECEPTOR

Answer 10

• Nicotinic Ach
  -NMJ motor neurone terminals release Ach that binds to receptors on Muscle membrane
• NAchR - Have an intrinsic ion channel
• Opening via the binding of 2x Ach
• Let’s Na+ and K+ flow through not anions
  Moves MP towards 0 intermediate betwe ENa and EK

Question 11

NAchR - Describe its features and non selectivity

Answer 11

• NAchR- Intrinsic ion channel, open via the binding of two Ach, channel lets Na+, K+ through
• Moves MP towards 0 intermediate between ENa and EK
• Nicotine also binds - so very active in smokers
• Opiates also bind such as morphine, cannabinoids such as Marijuana increase activity so effects muscle see SHAKES

Question 12

HOW DO WE CONTROL CHANNEL ACTIVITY?

ESPECIALLY THAT WE KNWO THAT MEMBRANE PERMEABILITY- THEREFORE CHANNEL ACTIVITY AFFECTS MP

Answer 12

• Channels can open or close- Gated
  3 types of gating
• Ligand eg NAchR and Serotonin receptors
• Voltage gated - channels involved in AP
• Mechanical - Mechanoreceptors receptors, carotid stretch receptors and hair cells in the inner ear

Question 13

What is ligand gating?

Answer 13

• Channels open and close in response to binding of a CHEMICAL ligand.
• E.g. Channels at synapse which respond to extracellular signals eg Ach and Serotonin
• Channels that respond to intracellular messengers

Question 14

What is Mechanical Gating:?

Answer 14

• Channels open and close in response to MEMBRANE DEFORMATION
• Channels in mechanoreceptors , carotid sinus receptors and hair cells in the inner ear

Question 15

What is Voltage gating?

Answer 15

• Open and close in response to changes in membrane potential
• e.g. channels involved in action potentials
• Propagation of a nerve signal at a synapse.

Question 16

Give an example of sensory mechanical gating

Answer 16

• Cochlear Fluid filled structure with hair cells within them
• In the cuticular plates there are a number of Na+ and K+ channels
• Stop the K+ channels from opening, depolarisation occurs , Vg Ca2+ opens , influx Calcium causes vesicles with NT ( dopamine and Dynorphin) fuse with bMEMBRANE close to Afferent nerve
• NT binds to receptor on post synaptic membrane which generates an AP which goes to CNS for interpretation

Question 17

Where can synaptic connections occur?

Answer 17

• Nerve cell- nerve cell
• Nerve cell - Muscle cell
• Nerve cell - gland cell
• Sensory celll - Nerve cell- e mechanoreceptors
  Synapse Chem transmitter release presynap binds to receptors post synaptic

Question 18

WHAT TYPES OF SYNAPTIC TRANSMISSION CAN WE HAVE?

Answer 18

-Fast and slow synaptic transmission

Question 19

What is Fast synaptic transmission?

Answer 19

• The receptor channel is also the ION CHANNEL
• eg NACHR - intrinsic ion channel activity
• Transmitter binding causes the channel to open

Question 20

What two types of synapse do we have?

Answer 20

• Excitatory synapses - Membrane depolarisation - Ach, Dopamine and Glutamate - Permeable to Na+, Ca2+- NAchR - Cations in general
• Inhibitory synapse- Membrane hyperpolarisation- GABA, and Glycine
• Permeable to K+ and Cl-

Question 21

Describe excitatory synapses:

Answer 21

• Excitatory transmitters open ligand gated channels which cause membrane depolarisation
• Can be permeable to Na+, Ca2+ , NAchR- cations in general
• RESULTING IN MEMBRANE POTENTIAL = EPSP
• Which has a longer time course than AP 20 milliseconds delayed propagation
• Graded with the amount of transmitter
• Transmitters include Dopamine , Glutamate and ACH

Question 22

What transmitters involved in EPSPs?

Answer 22

• Dopamine
• Ach
• Glutamate
  ( Transmitters open ligand gated channels which cause membrane depolarisation)

Question 23

Describe Inhibitory synapse

Answer 23

• Inhibitory transmitters open ligand gated channels which causes hyper-polarisation.
• Permeable to K+ and Cl_
• Transmitters GABA and glycine

Question 24

What transmitters are involved in IPSPs?

Answer 24

• GABA

- Glycine

Question 25

WHAT TWO PATTERNS ARE SEEN IN SLOW SYNAPTIC TRANSMISSION?

Answer 25

- 1. Direct G protein Gating: eg Cannabinoid receptor - Localise and quite rapid comp to 2. - Within the membrane - Gating via intracellular messengers - Throughout the cell , amplification by cascade - slower because ENZYME AND CASCADE INVOLVED

Question 26

WHAT TWO FACTORS AFFECT MEMBRANE POTENTIAL

Answer 26

1. CHANGES IN ION CONCENTRATION: - Most important changes in extracellular k+ - Some times altered in clinical situations- Hyperkalemia - End stage renal failure - Can alter membrane excitability - in the heart Hyperkalemia where RMP higher so Na+ channels are not activated affects depol= bradycardia - 2. Electrogenic pumps - Na/K+ ATPASE contributes few mV in some cells 5 mV making more negative - Sets up and maintains the ionic gradients required to generate MP

Question 27

Explain the role of Na+ K+ ATPASE

Answer 27

- it does not generate the mp - some cells it contributes directly to the MP generate few mV - making more negative - Indirectly through Active transport it setts up and maintains the ion gradients which generate the resting membrane potential.

Question 28

Insulin release process explain:

Answer 28

- 1.Blood glucose increased 2. Glucose transported in to beta cell via facilitated diffusion through a glucose transported 3. Elevated concentration of glucose within B cell causes ATP into cell via metabolism which bind to ATP sensitive cell - K+ ATP sensitive cell - Closes the channel so k+ can no no longer leave have depolarisation 4. Causes Vg Ca2+ channels to open which causes influx ca2+ - which causes vesicles containing insulin o fuse with the membrane and release Insulin in to the blood stream via exocytosis. 5. Insulin decreases blood glucose levels

Question 29

What drugs is used to treat type 2 diabetes and how does it work?

Answer 29

- Sulfonylureas - Widely used to treat type two diabetes. - Because they stimulate insulin secretion from pancreatic B cells - They act by binding to the SUR site of ATP sensitive K+ channels inducing channel closure causing the depolarisation - Does not work on type 2 diabetes because B cells destroyed

Question 30

Membrane potentials of the heart

Answer 30

NO CHLORIDE CHANNELS SO NO CHLORIDE IONS YoU HAVE THREE PHASES THE RAPID DEPOLARISATION WHERE FAST Na+ channels operate - The Plateu is caused by Calcium entry L type - Repolarisation The MP of the heart -90mv held at this point because Na+ and Ca2+ channels are closed

Question 31

Change in membrane potential in the anterior pituitary

Answer 31

- Calcium release is required for prolactin secretion TRH- Gq and IP3 causing Ca2+ release, calcium binds to calcium sensitive k+ channels calcium leaves have hyper-polarisation you then have another G protein which binds o the ERG channel prevents K+ leaving - Have depolarisation calcium channels open calcium in causes prolactin release