Hsf: Neuromodulation Of Cardiac Excitability

Front 1

The flexibility in cardiac activity is controlled by ____ and _____ _____ _____.

Back 1

-Parasympathetic and Sympathetic Nervous System

Front 2

Functions of Autonomic System (Heart)

Back 2

-Control Heart Rate
-Cardiac contractibility
-Blood Pressure

Front 3

2 Major Divisions of the Autonomic System

Back 3

-Sympathetic
-Parasympathetic

Front 4

What are the parasympathetic nerves mainly distributed?

Back 4

-SA and AV nodes
-Less to atrial muscle
-Very little to muscle

Front 5

Nicotinic ACh Receptor(def)

Back 5

(Named by its pharmacological bloc by nicotine)
-Integral non-selective cation channel that produces skeletal muscle depolarization

Front 6

______ ______ activity releases ACh which acts on a _______ receptor at the nerve-skeletal muscle junction.

Back 6

-Vagal nerve
-"muscarinic"

Front 7

The ______ ______ in the cardiac nodal tissues is a "muscarinic" receptor

Back 7

-ACh receptor

Front 8

What happens when ACh binds to the type 2 muscarininc ACh receptor in the heart?

Back 8

-G-proteins are activated

Front 9

What does the activation of G-proteins (activated by the ACh receptors in the heart) do?

Back 9

-Inhibits Adenylate cyclase (which produces cAMP)
-(in AV and SA nodal tissue) triggers the opening of an inwardly rectifying K channel (GIRK)

Front 10

Parasympathetic inhibition of adenylate cyclase counteracts the stimulation of this adenylate cyclase by the _________ ________ ________.

Back 10

-Sympathetic Nervous System

Front 11

What does the activation of GIRK (G-protein-coupled Inward Rectifier K channel) do?

Back 11

-Provides increased hyperpolarizing influence on the membrane potential, making it more difficult for pacemaker channels to depolarize the SA node to threshold
-Net Result: slowing down of heart rate

Front 12

What mechanism does the sympathetic nervous system control the electrical activity of the heart?

Back 12

-Through actions of the sympathetic nerves=innervates part of the heart, especially the ventricular muscle
-Chemical transmitters released into circulation by adrenal medulla

Front 13

The sympathetic nerves release the transmitter _______ and the adrenal medulla secretes _______ into the circulation.

Back 13

-Norepinephrine
-Epinephrine

Front 14

What do norepinephrine and epinephrine bind to?

Back 14

-Beta-adrenergic receptors expressed in cardiac cells
-Activates a biochemical signaling process

Front 15

Biochemical Process (Epinephrine and Norepinephrine)

Back 15

-An increase in the activity of the enzyme, Adenylate cyclase=catalyzes the transformation of intracellular ATP to cyclic AMP (cAMP)

Front 16

Role of cAMP (Sympathetic Control)

Back 16

-Directly increases the rate of activation of the pacemaker channels=increase of heart rate
-Increases the activity of protein kinase A (PKA)

Front 17

Role of protein kinase A (Sympathetic control)

Back 17

-Catalyzes phosphorylation of voltage-gated Ca2+ channels in AV/SA nodal cells, Purkinje fibers, and both atrial and ventriculat contractile cells

Front 18

What does increase sympathetic activity result in?

Back 18

-Increase in rate of blood pumping
-increase in amount of blood pumped per beat
-increase in blood flow

Front 19

Phosphorylation caused by protein kinase A (PKA-Sympathetic control)

Back 19

-Increases activity of Ca2+ channel-->large fraction of open Ca2+ channels-->larger Ca2+ influx into muscle cells--->muscle cells produce stronger muscle contraction

Front 20

What would an increase in Ca2+ do by itself?

Back 20

-Lengthen the ventricular action potential
-Heart may not leave enough time for ventricular filling
-Bad effect on amount of oxygenated blood pumped through circulatory system

Front 21

The increase in PKA activity by Beta-receptor activation also leads to phosphorylation of ____ ______.

Back 21

-I(k) channels

Front 22

I(k) channels (Sympathetic Control)

Back 22

-K Channels that help repolarize the ventricular action potential

Front 23

What does increased repolarization following PKA-mediated I(k) do?

Back 23

-Channel phosphorylation greatly reduces the ventricular action potential duration

Front 24

Overall Result of increased sympathetic nervous system activity on the heart

Back 24

-Increased heart rate
-Increased strength of contraction
-Reduced Action Potential

Front 25

How is the QT interval set?

Back 25

-In large part by the duration of ventricular action potential

Front 26

QT(c) (def)

Back 26

-the measured QT divided by the square root of the R-R interval(in sec)