Cardiac Signaling Pathways

Question 1

Quickly review the process of G-protein coupled receptor activation.

Answer 1

A ligand binds the 7-transmembrane-spanning receptor which changes the conformation, allowing it to associate with heterotrimeric G-proteins; the heterotrimeric G-protein changes conformation upon binding to the receptor and then switches GDP for GTP; this activates them and induces separation

Question 2

cAMP binds to the _______ of PKA.

Answer 2

regulatory subunits

Question 3

PKA phosphorylation of CaL induces __________.

Answer 3

slower inactivation, and hence increased inotropy

Question 4

PKA phosphorylation of RyR2 induces __________.

Answer 4

increased calcium sensitivity, and hence increased inotropy; also, more calcium release from the SR leads to more NCX activation and more gradual depolarization

Question 5

PKA phosphorylation of troponin I induces ___________.

Answer 5

decreased calcium affinity, which speeds up release and hence boosts lusitropy

Question 6

PKA phosphorylation of phospholambin induces __________.

Answer 6

decreased inhibition of SERCA, which increases inotropy and lusitropy

Question 7

What are HCN channels?

Answer 7

Hyperpolarization-activated cyclic nucleotide sensing channels

Question 8

How does norepinephrine effect a faster heart rate?

Answer 8

It binds to a stimulatory GPCR that leads to cAMP production; cAMP binds to an HCN that is part of the I(funny) current channels, causing them to open and depolarize faster.

Question 9

How does norepinephrine lead to a faster upstroke?

Answer 9

The cAMP produced by ß-adrenergic signals activates PKA and that phosphorylates CaL, leading to slower inactivation. (The extra calcium also stimulates the NCX, which leads to depolarization.)

Question 10

When acetylcholine binds to an M2 muscarinic receptor (part of the parasympathetic nervous system), it ___________.

Answer 10

activates an inhibitory G protein, which deactivates adenylate cyclase (undoing all that ß-adrenergic activation had done) and the ß/gamma subunit activates a potassium channel–which hyperpolarizes the cell

Question 11

Unlike striated muscle, smooth muscle is not ___________.

Answer 11

thin-filament regulated

Question 12

How is smooth muscle activated?

Answer 12

It does not require action potentials, but it does still need influx of calcium–which can occur from electrical, mechanical, or chemical stimulation. Calcium activates calmodulin, which binds to myosin light-chain kinase (MLCK), a protein that phosphorylates and thus activates myosin.

Question 13

In smooth muscle, norepinephrine binds to ___________.

Answer 13

a GPCR that leads to Gq activation, which activates PLC and leads to the release of IP3, which activates RyR

Question 14

What does activation of alpha adrenergic receptors do?

Answer 14

It leads to vasoconstriction mediated by Gq receptors

Question 15

Why is inhibition of TnI important?

Answer 15

Phosphorylation of TnI by PKA leads to decreased calcium sensitivity of TnC. Decreased sensitivity (by decreased affinity, I believe) leads to faster relaxation–important at higher contraction frequencies.

Question 16

There is little parasympathetic innervation of ____________.

Answer 16

the ventricles; thus, there is no parasympathetic control of inotropy

Question 17

Atropine blocks ___________.

Answer 17

the M2 muscarinic receptors

Question 18

HCN channels produce the __________.

Answer 18

funny current (I[funny]) which gradually depolarizes the cell

Question 19

HCN channels are stimulated by ___________.

Answer 19

sympathetic activation

Question 20

Parasympathetic innervation of the heart occurs through branches of the ______ nerve on the _______.

Answer 20

vagus; sinoatrial node

Question 21

What do the alpha and beta/gamma subunits of parasympathetic G proteins do?

Answer 21

The alpha subunit inhibits the adenylate cyclase that is stimulated by sympathetic nerves; the beta/gamma subunit activates the GIRK (G-protein-coupled Inward Rectifying K+), which hyperpolarizes the cell and slows the heart.

Question 22

Like cardiac myocytes, ______ are also connected by gap junctions.

Answer 22

vascular smooth muscle cells

Question 23

Smooth muscles contract based on ___________, unlike striated muscles which contract as an all-or-none response.

Answer 23

the strength of the signal

Question 24

Smooth muscle contraction is slower because it depends on the ____________.

Answer 24

phosphorylation of the myosin chain, which is a covalent reaction

Question 25

PKA promotes vasodilation by __________.

Answer 25

phosphorylating myosin light chain kinase

Question 26

The beta/gamma subunit of stimulatory G proteins ___________.

Answer 26

binds to and activates calcium channels