Flashcards in Adrenoceptors and the heart Deck (44):
Heart SNS receptors
B1, some a1 on contractility
Blood vessels SNS
Predominantly a1 for contraction, some B2 for relaxation.
Non-innervated B2 relax
M3 contract and increase secretion
GI tract SNS
Decrease motility (all except a2), sphincters contract and glandular cells decrease secretion (a2)
GI tract PNS
All M receptors; increase motility, sphincters relax, glands secrete.
B1; increase renin secretion
glucose release; a1 mediated.
radial muscle; a1 contracts.
Ciliary muscle; B2 relaxes
Lacrimal glands; a increases secretion.
M3 in eye
Cause contraction of sphincter muscle, ciliary muscle and increased secretion.
SNS in ejaculation
PNS in erection
M3 and NO
a1 intracellular cascade
Gq/11 --> PLC. Increased Ca++ and PKC activation via IP3 and DAG
a2 intracellular cascade
Gi/o; By directly inhibits VGCC. a decreases phosphorylation which inhibits VGCC
B receptor intracellular cascade
Gs; leads to cAMP (If current) and PKA rise (increase in VGCC activation and inactivation of MLCK)
Adrenaline on CVS
Increases heart rate, decreases TPR, increases BP slightly
Noradrenaline on CVS
Increase in TPR increases BP significantly, so baroreceptor reflex decreases heart rate.
Isoprenaline on CVS
Decrease in peripheral resistance, increase in heart rate, decrease in BP due to diastolic decrease.
B3 receptor in heart
Negative inotropic effect; possibly 'safety valve' for high [catecholamine].
Mimicking B1 stimulation in heart.
Use cholera toxin or forskolin.
Effect of B1 stimulation of heart.
increases cAMP so PKA so increases Ca++ entry;
1) Inotropic effect
2) Sensitises ryanodine receptors
3) PKA phosphorylates SERCA and phospholamban.
4) Chronotropic effect
5) Enhances effect of delayed rectifier K+ channels.
Effects of M2 stimulation on heart.
Negative chronotropic effect to due to decreased cAMP and PKA but not inotropic as confined to nodal tissue.
If activation shifted to more negative levels.
Ik-ACh hyperpolarises cell.
Na+ channels structure
a subunit forms pore; B to do with trafficking. Relatively TTX insensitive in the heart.
Channels with S4 charged TM domain on each subunit
NaV, CaV and Kv channels. voltage sensor
Inactivation loop between domain 3 and 4 and linker chain on 4.
a1 = pore. a2d and B = channel trafficking
Phosphorylation enhances sensitivity
Sensitive to Ca++ blockers.
only occur in nodal and conductive tissue, not in contractile tissue.
Kv channel mutations
Lead to episodic ataxia and long QT syndrome (latter also by NaV mutations).
Kv channels distribution
None in nodal tissue
Kv channel inactivation
N-type; N-terminal occludes.
C-type; movement of residues near extracellular surface.
Shaker K channels
Kir channels; role
maintenance of resting potential without loss of K+ during d'poln. Unknown in liver and kidney. Carry I(k1).
Kir channels; structure
2 transmembrane domains
Why do Kir channels close?
Due to Mg++ and polyamine (e.g. spermine) occlusion.
Inward rectifiers, ACh responsive, ATP-sensitive.
Kir channels; activated by By subunit on M2 stimulation; leads to hyperpolarisation.
ATP sensitive K+ channels; sulphonylureas
Sulphonylurea drugs close to stimulate insulin secretion
ATP sensitive K+ channels; smooth muscle
Opening causes relaxation; anti-hypertensive drug target.
ATP sensitive K+ channels; ATP
Closes. Also protects from ischaemia.