Missing From Phys Exam 1 (Starting From 229)

Front 1

autonomic regulation of excitation-contraction coupling

Back 1

activation of PKA through adenyl cyclase, leads to phosphorylation that INC Ca2+ availability, max dose of epinephrine will INC Ca2+ transient by 2-5 fold, more Ca2+ in cell, more can be reuptaken, if more reuptaken INC strength of the next contraction

Front 2

sympathetic stimulation and cardiac contraction

Back 2

can be used INC cardiac contraction through beta-adrenergic receptor stimulation, norepinephrine and epinephrine interact with these receptors that stimulate the production of cAMP through GTP-binding protein, leads to activation of PKA, PKA can then phosphorylate things

Front 3

what target proteins does PKA phosphorylate

Back 3

1. Ca2+ channels
2. RyR in the SR
3. phospholamban
4. troponin I

Front 4

what effect does phosphorylation have on Ca2+ channels

Back 4

enhances their open probability, this INC their efficacy as a trigger in CICR and SR Ca2+ store content, most important in INC the size of the Ca2+ transient and contraction

Front 5

what effect deos phosphoarylation have on RyR in the SR

Back 5

PKA stimulates the ability of Ca2+ influx to INC their activity and thus improves Ca2+ release, phosphorylation may also INC their inactivation to facilitate termination of Ca2+ release

Front 6

what effect does phosphorylation have phospholamban (PLB)

Back 6

associated with the SR Ca2+ ATPase, in dephosphorylated state, PL represses the activity of the pump, when phosphorylation of PL occurs, it relieves the inhibitory action on the pump and INC its pumping rate, enhances Ca2+ reuptake in the SR, INC rate of relaxation of the Ca2+ transient

Front 7

what effect does phosphorylation have on troponin I

Back 7

troponin I is a regulatory protein forming the troponin complex, phosphorylation reduces the affinity of the troponin complex fro Ca2+ which facilitates relaxation

Front 8

what is the first thing to happen when you have sympathetic nervous stimulation

Back 8

INC in heart rate, this causes an INC in Ca2+ ATPase activity

Front 9

sarcomere length and systole

Back 9

results in muscle shortening, results form the interaction between thin and thick filaments within the sarcomere

Front 10

acto-myosin bridge cycling

Back 10

pulls the two filaments against each other and thus shorten sthe distance between two Z lines

Front 11

myosin

Back 11

thick filament component, weights 480 kD, composed of two heavy chains and four light chains, responsible for ATP hydrolysis and interacts with actin, ATPase activity plays an essential role in contraction

Front 12

cardiac myosin heavy chain isoforms

Back 12

in the atria, there are A1 (very high ATPase) and A2 (low ATPase) variants, in the ventricles, there are V1 (high ATPase), V2 (intermediate ATPase), and V3 (low ATPase) isoforms

Front 13

heart failure and myosin structures

Back 13

in heart failure there is a shift in the expression of myosin from the V1 isoform to V3 (low ATPase activity), contributes to heart failure where there is DEC contractility, will reduce the rate of formation of actomyosin

Front 14

actin

Back 14

thin filament component, 41.7 kD, responsible for activating myosin ATPase and interacts with myosin, composed of F-actin proteins held together by disulfide bonds, monomer of actin is G-actin, spontaneously interacts with myosin heavy chains

Front 15

regulatory proteins

Back 15

tightly bound to the actin filaments and are responsible for the coupling of the intracellular Ca2+ transient ot acto-myosin bridge cycling, includes tropomyosin and the troponins

Front 16

tropomyosin

Back 16

thin filament component, 67 kD, composed of two nonidentical chains, responsible for moduclating actin-myosin interaction, lies in one of the two grooves formed by the two actin polypeptide chains, adds rigidity to the thin filament

Front 17

frequency of the troponin complex

Back 17

one complex every ~400 angstroms

Front 18

troponin C (TnC)

Back 18

thin filament component, 18 kD, composed of one component containing 4 EF hands, responsible for binding Ca2+, the end effector in EC coupling, dumbbell shaped with two opposing globular regions joined by a single 9 turn alpha-helix, has two divalent cation binding sites labeled I-IV, I and II are Ca2+ specific but only site II is considered the acceptor site, III and IV bind both Ca2+ and Mg2+ which stabilize the troponin complex

Front 19

troponin I

Back 19

located between TnC and TnT, thin filament component, 23 kD, responsible for inhibitng actin-myosin interactions but weaker than Tm, responsible for inhibiting acto-myosin bridge cycling during diastole, phosphorylated by PKA which enhances its ability to inhibit the interaction and accelerate relaxation

Front 20

troponin T

Back 20

thin filament component, 38 kD, responsible for binding troponin complex to the thin filament maintaining its structural activity, spans the length of several G-actin monomers, binds to both TnI and Tm

Front 21

diastole and thin filament regulation

Back 21

during diastole, Tm blocks the interaction between actin and myosin due to the pulling action exerted by the troponin complex on Tm when Ca2+ is not binding TnC

Front 22

systole and thin filament regulation

Back 22

binding of Ca2+ on sites I and II of TnC triggers the displacement of Tm deeper in the grooves of F-actin which exposes the myosin binding sites on actin

Front 23

molecular contraction cycle

Back 23

when Ca2+ concentrations are high, favors the spontaneous interaction of myosin and actin
step 1-ATP is bound to myosin and relieves the interaction between myosin and actin, ATP is then hydrolyzed rapidly by myosin ATPase, ADP and Pi are not release but remain bound to myosin, myosin is now in a relaxed, energized conformation
step 2-with ADP and Pi bound, favors binding of myosin to actin
step 3-ADP and Pi now dissociate causing a conformation change in the globular heads of myosin, this leads to shortening of the sarcomere through the sliding of actin and myosin filament over each other, causes rigor complex
step 4-rigor complex , relieved by binding of ATP and the cycle starts again

Front 24

what happens when ATP production is inhibited in cardiac contraction

Back 24

e.g. metabolic inhibition such as cardiac ischemia, leads to a state of hyperctonractility or stunning

Front 25

what determines the strength of cardiac contraction

Back 25

determined by the number and rate of cross-bridge formations, determined by the level of myosin ATPase activity

Front 26

length-tension relationship

Back 26

tension vs. sarcomere length, bell shaped curve for sarcomere length raning from ~1-3.5 microMeters, max tension at 1.8-2.2 microM sarcomere length, not tension at 3.65 micrometers (due to the fact that there is no overlap between the cross-bridge and thin filaments, muscle length follows the same relationship as sarcomere length, level of force will depend on the degree of overlap between the myosin globular head and actin filaments

Front 27

when is tension and contraction force at a max

Back 27

occurs when all cross-bridges are adjacent to thin filaments, occurs until the point when the thin filaments begin to overlap, this causes tension to fall

Front 28

relationship between ventricular volume and pressure

Back 28

inversely related

Front 29

What are the two ajor physcial factors that determine arterial pressure?

Back 29

arterial blood volume and arterial compliance

Front 30

What physiological factors affect arterial blood volume and arterial compliance

Back 30

heart rate, stroke volume, cardiac output and peripheral resistance

Front 31

What are the two physiological determinants of mean arterial pressure

Back 31

CO and total peripheral resistance

Front 32

what are the two physical determinants of the pulse pressure?

Back 32

arterial compliance and the change in arterial volume