Action potentials Flashcards
List the phases of action potential
Phase 0 = upstroke Phase 1 = early repolarisation Phase 2 = plateau Phase 3 = repolarisation Phase 4 = resting membrane potential
What happens in phase 0 in atria, ventricles, Purkinje fibres?
upstroke is brought about by fast increase in gNa
How are the Na channels in heart different to those in other excitable cells? what can (or cannot) inhibit them?
- Na channels with similar properties are also expressed in subsets of mammalian SAN and AVN cells
- Inhibited by tetrodotoxin, saxitoxin and local anaesthetics but…
- Biophysical and pharmacological properties of cardiac Na channels distinct from Na channels expressed in other excitable cells such as neurons and skeletal muscle
- Cardiac Na channels remarkably insensitive to tetrodotoxin (TTX) compared with neuronal Na channels
what mutations are seen in inherited long QT syndrome LQT3?
• Mutations in the gene, SCN5A, encoding the TTX-”insensitive” cardiac Na channels are seen in patients with an inherited form of long QT syndrome, LQT3
What happens in phase 1 in atria/ventricles/purkinje?
TRANSIENT OUTWARD CURRENT • Responsible for notch • Carried by K+ and Cl- • Ito composed of two (main) currents – Ito1 (current carried by OUTward K) – Ito2 (now ICl(Ca)) carried by INward Cl • Ito1 inhibited by 4-aminopyridine • Ito2 activated by Ca
What happens in phase 2 regarding Calcium in atria/ventricles/purkinje?
PLATEAU CURRENTS (1) CA CURRENT
• Trigger for CICR - activates ryanodine receptor
• Activates rapidly (within 2 ms) but a/p upstroke dependent more on INa
• Required for contraction
• Inactivation dependent on Em and [Ca]i
what can inhibit the phase 2 Ca channels?
• Inhibited by dihydropyridine Ca channel antagonists – Nifedipine – Nitrendipine – Nisoldipine • Inhibited by verapamil, Cd and Ni
What happens in phase 2 regarding Potassium in atria/ventricles/purkinje?
• Em does not change rapidly
• Achieved by balance of Ca influx (via L-type Ca channels) and K efflux (via three K channels)
– IKur ultrarapid (IKplateau)
– IKr rapid
– IKs slow
• Absence of large K efflux (via inward rectifier, IK1)
• Myocardial K currents function to control resting membrane potentials, duration of action potentials refractoriness, and automaticity.
list the K channels – delayed rectifers
what do you know about mutations?
- 6 transmembrane regions
- IKur = Kv1.5
- Ito = Kv1.4 Kv4.2
- IKs = KvLQT (KCNQ)
- IKr related to Drosophilia gene product that makes the flies legs wobble when anaesthetized with ether (ether-a-go-go) – eag; human counterpart called HERG
- Mutations in IKs or IKr cause congenital long QT syndrome
describe the K channels – inward rectifiers
- Inward rectifying K channels generally abbreviated Kir
- 2 transmembrane segments (M1 and M2)
- Unusual rectification reflects lack of S4 region
- IK1 = Kir2.1
- IK,ACh = Kir3.1 & 3.4
- IK,ATP = Kir6.2
What happens in phase 3 in atria/ventricles/Purkinje?
- Initial phase of repolarization brought about by IKs
* Negative to –30mV IK1 most important
what happens to excitability in myocardial infarction?
Myocardial infarction –>K loss from cells –> Increased IK1 &depolarisation –>more INa needed to offset & reduces number of Na channels available (inactivation) –>excitability reduced
what other currents are present?
• INa/Ca can produce inward and outward current
• IK,ATP (requires Kir6.2 and SUR – sulphonylurea receptor)
– Activated by increase in [ADP]/[ATP] ratio i.e. in hypoxia/ischaemia, nicorandil, pinacidil, cromakalim
– Inhibited by glibenclamide, tolbutamide
• IK,ACh is inward rectifier prominent in SA and AV nodes – heterotetrameric in structure; two Kir3.1 and two Kir3.4 molecules
– Activated on parasympathetic activity
– Stabilizes Em near EK
describe the pacemaker current
• Pacemaker current termed If for “funny” current
• Called “funny” for two reasons:
– Activates slowly on hyperpolarization opposite to most voltage-gated channels
– If not selective between Na and K (though Erev is ~ -15mV so at more negative membrane potentials inward current carried by Na)
• Cloned channel belongs to HCN class (Hyperpolarization-activated Cyclic Nucleotide gated)
• Funny channels are also found in Purkinje cells (this allows the Purkinje cell to show some degree of pacemaker activity)
what currents are present or absent in the SA node?
- Most channels exist in SA node – to some extent
- Exception is IK1 – no IK1 in SA node
- Very little INa – upstroke produced by ICa
- Also T-type Ca channels that activate earlier (more negative potentials than L-type)
- Ito is very small
- IK is main repolarizing current
- If and IK,ACh present
- Upstroke produced by ICa
- After pacemaker potential; upstroke can be completely inhibited by blocking ICa
