Week 4 - Cellular and Molecular Events in the CVS Flashcards
How is the resting membrane potential generated?
It is largely due to K+ permeability of the cell membrane at rest
- Leaky K+ channels are open at rest
- Only small permeability to other ions
- K+ ions move out of the cell, down their concentration gradient
- This small movement of ions makes the inside negative with respect to the outside
- This negative charge can attract K+ ions, so they will not leave the cell
- As charge builds up, an electrical gradient is established
- There is a net outflow of K+ until Ek+ is reached
Na+/K+ ATPase establishes the gradient, but it doesn’t set it
How do cardiac muscles cell cause contraction?
They are electrically active
- They fire action potentials
- The action potential triggers an increase in cytosolic [Ca2+]
- A rise in calcium is required to allow actin and myosin interaction, which generates the contraction
Explain the changes in membrane potential of ventricular cells over the cardiac cycle
- Resting membrane potential (about -75mV) is due to background K+ channels
- Increase (to about +30mV) is due to opening of voltage-gated Na+ channels and hence an influx of Na+
- Initial repolarisation (to about +10mV) is due to transient outward K+ channels, and hence an efflux of K+
- The decrease in membrane potential plateaus due to the opening of voltage-gated Ca2+ channels and hence an influx of Ca2+, which is balanced with K+ efflux (to about -20mV)
- Repolarisation (to RMP) is due to efflux of K+ through voltage-gated K+ channels and others. At this stage, Ca2+ channels have been inactivated
Explain the changes in membrane potential of pacemaker cells over the cardiac cycle
Pacemaker potential
- Initial slope to the threshold (gradual depolarisation)
- Activated by membrane potentials more negative than -50mV (the more negative it is, the more it activates)
- Uses HCN channels (and voltage-gated Na+ channels), so there is an influx of Na+
Upstroke
- Opening of voltage-gated Ca2+ channels (Ca2+ moves in) and release of Ca2+ from intracellular stores
Downstroke
- Opening of voltage-gated K+ channels (efflux of K+)
What are HCN channels?
Hyperpolarisation-activated, cyclic nucleotide-gated channels
- Allow influx of Na+
What is the role of the sinoatrial node?
It is the fastest to depolarise, so it sets the rhythm and acts as the pacemaker
What is the structure of a cardiac myocyte?
- Single central nucleus
- Cells are mechanically joined at intervertebral disks by desmosomes
- There are gap junctions, which permit movement of ions and electrically couple cells
How is cardiac myocyte contraction regulated?
In the same way as skeletal muscle:
- Ca2+ binds to troponin C
- Conformational change shifts tropomyosin to reveal myosin binding site on actin filament
- Sliding filament theory
How are cardiac monocytes relaxed?
Intracellular [Ca2+] must return to resting levels
- Most is pumped back into the sarcoplasmic reticulum be SERCA
- The raised [Ca2+] stimulates the pumps
- Some exits across the cell membrane via the Na+/Ca2+ exchanger or sarcolemmal Ca2+ ATPase
How is the tone of blood vessels controlled?
By contraction and relaxation of vascular smooth muscle cells
- Located in the tunica media
- Present in arteries, arterioles and veins
How is contraction of vascular smooth muscle regulated?
Ca2+ binds to calmodulin
- This activates myosin light chain kinase
- This phosphorylates the myosin light chain to permit interaction with actin
Relaxation as Ca2+ levels decline
- Myosin light chain phosphorylase deactivates the myosin light chain
Phosphorylation by protein kinase A inhibits myosin light chain kinase, hence inhibiting contraction
What initiates contraction of vascular smooth muscle cells?
Depolarisation/activation of alpha-adrenoceptors
What does the autonomic nervous system exert control over?
- Smooth muscle (vascular and visceral)
- Exocrine secretion
- Rate and for of contraction of the heart
What are the divisions of the autonomic nervous system?
- Parasympathetic
- Sympathetic
- Some include a 3rd division, enteric (a network of neurones surrounding the GI tract)
What is the autonomic nervous system important for?
Regulating many physiological functions:
- Heart rate, blood pressure, body temperature, etc.
- Coordinates the body’s response to exercise and stress
Describe the origin and synapse of sympathetic nerves
- Thoracolumbar origin
- Preganglionic neurones arise from segments T1 to L2
- Most synapse with postganglionic neurones in the paravertebral chain of ganglia
- Some synapse in a number of prevertebral ganglia
Describe the origin and synapse of parasympathetic nerves
- Craniosacral origin
- Preganglionic fibres travel in cranial nerves or sacral outflow from S2-S4
- Synapse with neurones in ganglia close to the target tissue
- Short postganglionic neurones
What chemical transmitters and receptors are used in sympathetic neurones?
- Between pre- and post-ganglionic: acetylcholine, with nicotinic ACh receptors
- Between post-ganglionic and target tissue: noradrenaline, with adrenergic receptors
- But sympathetic input to sweat glands in mainly cholinergic (post-ganglionic neurones release ACh which acts on muscarinic ACh receptors)
What chemical transmitters and receptors are used in parasympathetic neurones?
- Between pre- and post-ganglionic: acetylcholine, with nicotinic ACh receptors
- Between post-ganglionic and target tissue: acetylcholine, with muscarinic ACh receptors
Describe muscarinic ACh receptors
- G-protein coupled receptors (M1, M2, M3)
- No integral ion channel