Autonomics in heart regulation Flashcards
Phospholamban (PLB)
reg. protein affects SR Ca pumps; when phosphorylated is inactive, but when not phosphorylated inhibits the activity of SR Ca;
PKA phosphorylates it (cAMP activated - Gs activated - beta adrenergic receptor)
Mitochondrial Metabolism Regulation
by the Ca transient; taken in by a uniporter and removed by NCX; rise in Ca in mitochondria stimulates Ox. Phos.
Autonomic innervation of the heart
Sympathetic system totally innervates; parasympathetic system only innervates the atria
Autonomic neurotransmitters
ACh from Parasympathetics, NE from sympathetics, Epi from adrenal medulla
Adrenergic receptors in the heart
Beta-1 and alpha receptors. Beta-1 can compete with alpha receptors for NE
Dromotropic effect
increase in conduction velocity through the heart
Catecholamine effect on AP curve
the plateau is raised (greater amplitude) but shortened (shorter wavelength)
PKA effect (catecholamine) on myocytes
Targets:
1) Iks receptors - more likely to be open, shorten AP
2) Troponin - better ability to release Ca from TropC, speed up relaxation
3) PLB - inhibits the inhibitor of SR Ca pump; more SR Ca available, faster clearance
4) L-type Ca channels - greater influx of Ca - faster depol. and more depol.
Beta-blockers
treatment for those with compromised coronary circulation - inhibits catecholamine response
Ouabain effect
Increases contraction without raising HR. Actually decreases HR slightly, as the Parasymp. system reacts to increased SV.
Inhibitory effects of ACh
from Vagal trunk (so only to Atria): stimulates Gi (inhibitory on adenylyl cyclase) and the opening of G-activated inward rectifier channels (GIRK or K-ACh); hyperpolarizes SA cells = AP’s drop lower
Gi protein subunits and their activities
beta/gamma subunits affect GIRK; alpha subunit inhibits adenylyl cyclase; Open GIRK creates lengthening of the wave for Sinoatrial AP’s; negative chronotropic effect; also atrial contraction is decreased = negative inotropic effect
Metabolic factors
metabolic compromise leads to lower pH. Lower pH decreases tropC’s affinity for Ca, opens K channels and closes Ca channels; also activates adenosine release which acts in the same manner as ACh on the heart
ACh effect after stomach punch
heart stops beating for a few seconds
Catecholamine effect pacemaking cells
1) Up-regulation of L-type Ca channels = faster depol.
2) Up-regulation of F-type background cation channels = faster depol, higher resting mem. potential
3) Up-regulation of NCX (secondary to up-regulation of L-type Ca channel) = faster depol.
ACh effect in ‘working atrium’
negative inotropic effect as GIRK’s shorten the duration of L-type opening and cause a drop in the transient Ca
ACh effect in ventricles
ACh can partially reverse the effects of NE or Epi (catecholamines) but this effect is negligible at its strongest
Carbachol
agonist of muscarinic (metabotropic) ACh receptors; hyperpolarizes cardiac cells (stops atrial arrhythmia) but also causes urination and sweating - ACh activation
ROMK
Renal Outer Medullary Potassium channel; one of the IRK channels
cAMP and Iks/Ikr
Iks is activated by cAMP, but Ikr is not; this is relevant in catecholamine stimulation of the SA node, wherein there are no Iks receptors, meaning that there is no shortening of the repolarization wave in sympathetic stimulation of the SA node
Location of Ito channels
epicardial myocytes and Purkinje fibers (responsible for phase 1 peak)
ENAC
epithelial sodium channel
L-type vs. N-type Ca channels
L-type located in myocytes and arterioles. Only relevant in cardiac myocytes. Can be blocked by DHP’s like nifedipine. Arterioles have 10x affinity for nifedipine than cardiac L-type;
N-type is neuronal and deals with neurotransmitter release
Chloride channels
CLC channels maintain electroneutrality in cells when protons are pumped in to acidify the cytoplasm
CFTR channels secrete NaHCO3 in pancreatic duct, NaCl into gut and absorb NaCl from sweat duct
Cl channels that move Cl into sweat duct respond to rises in cytoplasmic Ca
Ligand gated - not responsible for (IPSPs)
