Voltage Gated Ion Channels

Question 1

what are voltage-dependent ion channels?

Answer 1

membrane proteins that conduct ions at high rates

regulated by voltage across membrane

Question 2

what do voltage dependent ion channels play a fundamental role in?

Answer 2

generation + propagation of nerve impulse in cell homeostasis

Question 3

what is the voltage sensor?

Answer 3

region of protein bearing charged AA

relocate upon chains in membrane electric field

Question 4

what does the movement of the sensor initiate?

Answer 4

conformational change in gate of conducting pathway

thus controlling flow of ions

Question 5

voltage gated Na+ channels

Answer 5

have 2 voltage sensitive gates

• at resting Em, one gate closed + other open
• when membrane depolarised, second gate opens
• after short time, second gate shuts

Question 6

how may drugs affect the na+ channels in nerves?

Answer 6

• involved with AP
• local anaesthetics - lidocaine
• block channel + reduce pain

Question 7

how may drugs affect the na+ channels in the heart?

Answer 7

• involved in generation of cardiac AP

- drugs can block na+ channels in arrhythmias

Question 8

what does tetrodotoxin (TTX) block?

Answer 8

AP by binding to na+ channels

Question 9

where is TTX found?

Answer 9

in puffer fish, toads, newts, blue ringed octopus

Question 10

what does TTX poisoning cause?

Answer 10

paralysis of voluntary muscles (diaphragm)

breathing stops

loss of vagal regulation of heart rate + loss of sensation

numbness of lips + tongue

Question 11

voltage gated k+ channels

Answer 11

only have one gate

gate activated by depolarisation

gate responds slower

Question 12

what is the function of the k+ channels?

Answer 12

membrane depolarisation

inhibition of k+ flux —> long QT syndrome

Question 13

black mamba snake venom + VGCs

Answer 13

• k+ channel blocker
• prevents repolarisation of nerve + muscle cells
• inc release of neurotransmitters
• prevents relaxation of muscle cells

Question 14

describe the structure of voltage gated calcium channels (VGCC)?

Answer 14

• have diff subunits: alpha1, alpha2-delta, beta1-4, gamma
• alpha1 forms ion conducting pore
• subunits = target of drugs

Question 15

what do voltage gated calcium channels include?

Answer 15

• neural N type channel blocked by w-conotoxin
• R type channel involved in poorly defined processes in brain
• closely related P/Q type channel blocked by w-agatoxins
• dihydropyridine-sensitive L-type channels responsible for excitation-contraction coupling of skeletal, smooth + cardiac muscle
• & for hormone secretion in endocrine cells

Question 16

L-type ca2+ channels + smooth muscle contraction

Answer 16

• smooth muscle cell depolarised
• L-type calcium channels open
• influx of extracellular ca2+
• calmodulin binds
• activated calmodulin activates myosin light chain kinase
• phosphorylates myosin
• myosin forms cross bridges with actin
• smooth muscle fibre contracts

Question 17

how may depolarisation be brought about?

Answer 17

• stretching of cell
• agonist binding G protein coupled receptor
• autonomic nervous system stimulation

Question 18

what are DHPs used as?

calcium channel blockers

Answer 18

vasodilators in treatment od hypertension

Question 19

what are verapamil and diltiazem used in?

calcium channel blockers

Answer 19

treatment of angina + arrhythmias

can depress cardiac function