Pharmacology - Cardiac & Arrythmias Flashcards
Cell membrane potential - 3
- Electrical events in cells are created by movement of charged ions across a semipermeable cell membrane.
- There are more negative charges inside the cell compared to the cell exterior.
- Hence, when voltage is measured inside the cell, it displays negative values measured in mV, & is commonly referred to as a cell membrane potential.
About ion driving forces - 5
- electrical negativity inside the cell that attracts positive ions
- Chemical [gradient] for a given ion between the cell interior & the exterior.
- The [gradients] for K+ & for Na+ & Ca++ oppose one another
- Efflux of K+ outside the cell is opposed by intracellular electronegativity.
- Influx of Na+ & Ca++ is assisted by intracellular electronegativity.
Ions transport - 3
- through ion channels (driven by both [gradient] for an ion & degree of cell electronegativity)
- By active transport (by ATP-driven pumps against [ion] gradients)
- by ion transporters & ion exchangers (driven by [ion[ gradients)
Selective vs non-selective Ion channels
- selective (permeable to only one ion, e.g. sodium channels, potassium channels, calcium channels)
- non-selective (permeable to more than one ion, e.g. Na+/K+)
Ion channels can be controlled by - 6
- Neurotransmitters (ligand-gated ion channels, e.g. nicotinic cholinergic receptor)
- Membrane voltage (voltage-activated ion channels)
- Receptor-coupled (metabotropic ion channels)
- Various ligands (e.g. cAMP, ATP, intracellular calcium ions)
- Other factors (e.g. mechanical stretch)
- Constitutively active (e.g. background potassium channels)
Cell resting potential - 9
- At rest cell membrane is mostly permeable to K+ ions
- K+ leaves via potassium channels [down] gradient, increasing electronegativity
- K+ efflux aided by [K+] gradient, oppose to electronegativity
- Na-pump maintain K+ & Na+ [gradients]
- Na-pump is electrogenic & maintains electrical negativity inside cells by removing excess Na+
- At rest, K+ efflux through K+ channels, maintains electronegativity
- Hence a negative basal membrane potential in majority of cells
- Many cells also permeable to Na+ at rest. Na+ influx reduces electronegativity inside the cell
- Results in less negative resting potential
Membrane depolarisation - 5
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).
Membrane repolarisation - 5
- In most AP depolarisation is short-lived & followed by repolarization
Two processes are involved, both stimulated by membrane depolarisation: - Increased K+ efflux through voltage-activated potassium channels
- Decreased Na+ influx due to closure of fast Na+ channels (inactivation) whilst depolarised.
- Cell is repolarised, & basal membrane potential is restored
- Na+ & K+ gradients restored by activity of the Na-pump
Define Refractoriness
Refractoriness: inability to generate 2nd AP in response to next stimulus
Two types of refractoriness
Two types of refractoriness:
1. Absolute (no AP will occur)
- Relative (a stronger stimulus can evoke the 2nd AP before cell is fully repolarised)
Refractoriness: Main mechanistic - 3
- Inactivation of fast sodium channels triggered by depolarisation.
- Inactivated sodium channels cannot be re-opened the 2nd depolarising stimulus.
- Sodium channels should recover from inactivation (occurs during repolarisation phase).
Partial Refractoriness - 3
1.Most Na channels are inactivated (absolute refractoriness)
2. Na channels are partly recovered (relative refractoriness)
3. Na channels are fully recovered (no refractoriness)
Functional relevance of Refractoriness - 5
- Refractoriness determines AP duration, hence regulating the frequency of Aps
- Longer the refractoriness, slower rate of AP generation.
- In skeletal muscles & heart, refractoriness determines rate of muscle contractions.
- In skeletal muscles, AP are short & at high AP rate individual contractions add together causing a sustained contraction of muscle.
- In the heart, cardiac AP has a plateau phase that increases AP duration, hence increases refractoriness of the heart.
Cardiac AP: 2
Cardiac AP:
1. In contractile atrial & ventricular myocytes & Purkinje fibers
2. Defines heart rhythm, regulates heart rate, controls force of the heartbeat
Pacemaker AP: 3
Pacemaker AP:
1. In pacemaker cells of the SA & AV Nodes
2. Sets heart rate (SAN)
3. Controls the rate of heartbeat (AVN)