Week 4 - Cellular and Molecular Events in the CVS Flashcards
(52 cards)
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
Describe adrenoreceptors
- G-protein-coupled receptors, which have no integral ion channel
- Types and subtypes: alpha (a1 and a2) and beta (b1 and b2)
- Different tissues can have different subtypes (allows of diversity of action and selectivity of drug action)
How do the sympathetic and parasympathetic nervous systems work together?
They work together to maintain a balance
- Sympathetic activity is increased under stress
- Parasympathetic activty is more dominant under basal conditions
- But sympathetic drive to different tissues is independently regulated
- Most organs are innervated by the sympathetic nervous system, some have both (which generally oppose each other)
Describe the sympathetic and parasympathetic effect + transmitter/receptor on the airway of the lungs
- Sympathetic: adrenaline, beta-2, relaxation
- Parasympathetic: ACh, M3, contraction
Describe the sympathetic and parasympathetic effect + transmitter/receptor on sweat glands
Sympathetic:
- Localised secretion: alpha-1, adrenaline
- Generalised secretion: M3, ACh
No parasympathetic effect
