Pharmacology - Cardiac & Arrythmias Flashcards

1
Q

Cell membrane potential - 3

A
  1. Electrical events in cells are created by movement of charged ions across a semipermeable cell membrane.
  2. There are more negative charges inside the cell compared to the cell exterior.
  3. Hence, when voltage is measured inside the cell, it displays negative values measured in mV, & is commonly referred to as a cell membrane potential.
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2
Q

About ion driving forces - 5

A
  1. electrical negativity inside the cell that attracts positive ions
  2. Chemical [gradient] for a given ion between the cell interior & the exterior.
  3. The [gradients] for K+ & for Na+ & Ca++ oppose one another
  4. Efflux of K+ outside the cell is opposed by intracellular electronegativity.
  5. Influx of Na+ & Ca++ is assisted by intracellular electronegativity.
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3
Q

Ions transport - 3

A
  1. through ion channels (driven by both [gradient] for an ion & degree of cell electronegativity)
  2. By active transport (by ATP-driven pumps against [ion] gradients)
  3. by ion transporters & ion exchangers (driven by [ion[ gradients)
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4
Q

Selective vs non-selective Ion channels

A
  1. selective (permeable to only one ion, e.g. sodium channels, potassium channels, calcium channels)
  2. non-selective (permeable to more than one ion, e.g. Na+/K+)
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5
Q

Ion channels can be controlled by - 6

A
  1. Neurotransmitters (ligand-gated ion channels, e.g. nicotinic cholinergic receptor)
  2. Membrane voltage (voltage-activated ion channels)
  3. Receptor-coupled (metabotropic ion channels)
  4. Various ligands (e.g. cAMP, ATP, intracellular calcium ions)
  5. Other factors (e.g. mechanical stretch)
  6. Constitutively active (e.g. background potassium channels)
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6
Q

Cell resting potential - 9

A
  1. At rest cell membrane is mostly permeable to K+ ions
  2. K+ leaves via potassium channels [down] gradient, increasing electronegativity
  3. K+ efflux aided by [K+] gradient, oppose to electronegativity
  4. Na-pump maintain K+ & Na+ [gradients]
  5. Na-pump is electrogenic & maintains electrical negativity inside cells by removing excess Na+
  6. At rest, K+ efflux through K+ channels, maintains electronegativity
  7. Hence a negative basal membrane potential in majority of cells
  8. Many cells also permeable to Na+ at rest. Na+ influx reduces electronegativity inside the cell
  9. Results in less negative resting potential
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7
Q

Membrane depolarisation - 5

A

1, Activation (opening) of fast sodium channels by a stimulus
2. causes rapid Na+ influx (assisted by gradient & cell electronegativity).
3. Build-up of Na+ reduces electrical negativity inside the cell.
4. Membrane potential becomes less negative, & the cell becomes depolarised.
5. At the peak of the AP cell interior can become even more positive than the cell exterior (AP overshoot).

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8
Q

Membrane repolarisation - 5

A
  1. In most AP depolarisation is short-lived & followed by repolarization
    Two processes are involved, both stimulated by membrane depolarisation:
  2. Increased K+ efflux through voltage-activated potassium channels
  3. Decreased Na+ influx due to closure of fast Na+ channels (inactivation) whilst depolarised.
  4. Cell is repolarised, & basal membrane potential is restored
  5. Na+ & K+ gradients restored by activity of the Na-pump
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9
Q

Define Refractoriness

A

Refractoriness: inability to generate 2nd AP in response to next stimulus

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10
Q

Two types of refractoriness

A

Two types of refractoriness:
1. Absolute (no AP will occur)

  1. Relative (a stronger stimulus can evoke the 2nd AP before cell is fully repolarised)
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11
Q

Refractoriness: Main mechanistic - 3

A
  1. Inactivation of fast sodium channels triggered by depolarisation.
  2. Inactivated sodium channels cannot be re-opened the 2nd depolarising stimulus.
  3. Sodium channels should recover from inactivation (occurs during repolarisation phase).
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12
Q

Partial Refractoriness - 3

A

1.Most Na channels are inactivated (absolute refractoriness)
2. Na channels are partly recovered (relative refractoriness)
3. Na channels are fully recovered (no refractoriness)

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13
Q

Functional relevance of Refractoriness - 5

A
  1. Refractoriness determines AP duration, hence regulating the frequency of Aps
  2. Longer the refractoriness, slower rate of AP generation.
  3. In skeletal muscles & heart, refractoriness determines rate of muscle contractions.
  4. In skeletal muscles, AP are short & at high AP rate individual contractions add together causing a sustained contraction of muscle.
  5. In the heart, cardiac AP has a plateau phase that increases AP duration, hence increases refractoriness of the heart.
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14
Q

Cardiac AP: 2

A

Cardiac AP:
1. In contractile atrial & ventricular myocytes & Purkinje fibers
2. Defines heart rhythm, regulates heart rate, controls force of the heartbeat

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15
Q

Pacemaker AP: 3

A

Pacemaker AP:
1. In pacemaker cells of the SA & AV Nodes
2. Sets heart rate (SAN)
3. Controls the rate of heartbeat (AVN)

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16
Q

The Cardiac AP is divided into 5 phases.

A

Phase 0: Rapid depolarisation
Phase 1: Rapid repolarization
Phase 2: Plateau
Phase 3: Repolarisation
Phase 4: Baseline

17
Q

Main types of ion channels which contribute to different phases of the Cardiac AP include - 5

A
  1. Phase 0: Rapid depolarization: Fast voltage-activated sodium influx
  2. Phase 1: Rapid repolarization: Transient potassium efflux & chloride influx (increase electronegativity)
  3. Phase 2: Plateau: A slower L-type voltage-activated calcium influx is balanced by voltage-activated potassium efflux thus maintaining the plateau
  4. Phase 3: Repolarisation: Several voltage-activated potassium channels
  5. Phase 4: Baseline (stable): Active background potassium efflux
18
Q

Refractoriness: Therapeutics - 3

A
  1. Block voltage-activated potassium channels in repolarisation phase 3, hence a longer AP duration (e.g. anti-arrhythmic Class III drugs);
  2. Reduce a number of available voltage-activated sodium channels, hence slowing down the rate of depolarisation phase 0 (termed Vmax) (e.g. anti-arrhythmic Class I drugs)
  3. Refractoriness can be reduced by drugs that block:
    Voltage-activated calcium channels during plateau phase 2 (e.g. anti-arrhythmic Class IV drugs)
19
Q

Phases of the Pacemaker AP: 0,3,4

A

Phase 0: Slow depolarisation: Slow onset of the AP

No phase 1 or plateau present

Phase 3: Repolarisation

Phase 4: Baseline (unstable): Spontaneous depolarisation

20
Q

Ion fluxes in the Pacemaker AP:
0, 3, 4

A

Phase 0: Slow depolarisation: Slow voltage-activated L-type calcium influx

Phase 3: Repolarisation: Voltage-activated potassium efflux

Phase 4: Pacemaker potential: Most important is sodium influx via non-selective cation channels (‘funny’ current). Little background potassium efflux.