Autonomics in heart regulation

Question 1

Phospholamban (PLB)

Answer 1

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)

Question 2

Mitochondrial Metabolism Regulation

Answer 2

by the Ca transient; taken in by a uniporter and removed by NCX; rise in Ca in mitochondria stimulates Ox. Phos.

Question 3

Autonomic innervation of the heart

Answer 3

Sympathetic system totally innervates; parasympathetic system only innervates the atria

Question 4

Autonomic neurotransmitters

Answer 4

ACh from Parasympathetics, NE from sympathetics, Epi from adrenal medulla

Question 5

Adrenergic receptors in the heart

Answer 5

Beta-1 and alpha receptors. Beta-1 can compete with alpha receptors for NE

Question 6

Dromotropic effect

Answer 6

increase in conduction velocity through the heart

Question 7

Catecholamine effect on AP curve

Answer 7

the plateau is raised (greater amplitude) but shortened (shorter wavelength)

Question 8

PKA effect (catecholamine) on myocytes

Answer 8

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.

Question 9

Beta-blockers

Answer 9

treatment for those with compromised coronary circulation - inhibits catecholamine response

Question 10

Ouabain effect

Answer 10

Increases contraction without raising HR. Actually decreases HR slightly, as the Parasymp. system reacts to increased SV.

Question 11

Inhibitory effects of ACh

Answer 11

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

Question 12

Gi protein subunits and their activities

Answer 12

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

Question 13

Metabolic factors

Answer 13

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

Question 14

ACh effect after stomach punch

Answer 14

heart stops beating for a few seconds

Question 15

Catecholamine effect pacemaking cells

Answer 15

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.

Question 16

ACh effect in ‘working atrium’

Answer 16

negative inotropic effect as GIRK’s shorten the duration of L-type opening and cause a drop in the transient Ca

Question 17

ACh effect in ventricles

Answer 17

ACh can partially reverse the effects of NE or Epi (catecholamines) but this effect is negligible at its strongest

Question 18

Carbachol

Answer 18

agonist of muscarinic (metabotropic) ACh receptors; hyperpolarizes cardiac cells (stops atrial arrhythmia) but also causes urination and sweating - ACh activation

Question 19

ROMK

Answer 19

Renal Outer Medullary Potassium channel; one of the IRK channels

Question 20

cAMP and Iks/Ikr

Answer 20

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

Question 21

Location of Ito channels

Answer 21

epicardial myocytes and Purkinje fibers (responsible for phase 1 peak)

Question 22

ENAC

Answer 22

epithelial sodium channel

Question 23

L-type vs. N-type Ca channels

Answer 23

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

Question 24

Chloride channels

Answer 24

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)

Question 25

Leak channels

Answer 25

the reason that resting potential is a little above Ek

Question 26

Nicotinic receptors

Answer 26

ACh mediated non-selective cation channels responsible for depolarization at the synaptic junction of muscular tissue

Question 27

I-F channels (F current)

Answer 27

non-selective cation channels that open when the cell is hyperpolarized, to help get the cell to the normal resting potential
can be activated by cAMP

Question 28

RyR

Answer 28

in skeletal muscle are triggered by DHP sensor movement

in cardiac cells are opened by the Ca transient and are responsible for Ca-induced Ca release

Question 29

IP3 Ca release channels

Answer 29

GPCR’s can activate PLC to cleave PIP2 into IP3 and DAG; IP3 activates ER Ca channels

Question 30

diastasis

Answer 30

slow ventricular filling

Question 31

percent of diastole taken up by rapid ventricular filling

Answer 31

25%