Chapter 3: Excitation Contraction (EC) Coupling: Calcium, the EC Powerhouse Flashcards
Cardiac myocyte
The functional unit of the pumping mechanism of the heart
Components of cardiac myocyte
- Sarcolemma (cell membrane)
- Sarcomere (containing the components necessary to contract and relax the cell)
- Mitochondria
- Sarcoplasmic reticulum (SR)
T -tubules
Deep invaginations of the sarcolemma
Function of T-tubules
Allow intimate coupling of the sarcolemma (containing calcium channels) with the SR (containing intracellular stores f Ca2+)
Separation of individual cardiac cells + function
Separated by intercalated disks (containing gap junctions) that allow for the passage of electrical activity
Components of myofibrils in cardiac myocytes
- actin (main component of thin filament along with proteins troponin and tropomyosin)
- myosin (thick filament)
Function of myosin
Pivoting head forms cross-bridges to actin filaments
Cross bridge cycling
- ATP fueled
- formation and breakage of cross-bridges
Caciums role in contraction-relaxation cycle
- Calcium binds to troponin which results in exposure of myosin binding sites and initiates and maintains cross-bridge cycling that leads to contraction
- In absence of calcium (between contractions when Ca2+ is pumped out) troponin and tropomyosin bind to actin ensuring relaxation
Two mechanisms of calcium entry into the cell
1) The sodium-calcium exchanger (moves 3 Na+ out of the cell for every 1 Ca2+ into the cell during systole)
2) Voltage gated L–type Ca2+ in cell membrane
Dyad
Microdomain consisting of SR and adjacent T tubule
Where Ca2+ induced Ca2+ release occurs
Calcium-induced calcium release
After the movement of Ca2+ across the sarcolemma (by 2 mechanisms) the concentration of Ca2+ in the microdomain/dyad rises to point where it is sufficient to open the Ca2+ release channels in the SR
Relaxation steps
- Ca2+ transport back into SR by SR Ca2+ pump
- once inside bound to calsequestrin
- held in terminal pockets (cisternae) of the SR so readily available for next AP - Ca2+ moved back across he sarcolemma by:
i) Ca2+ pump
ii) Na+/Ca2+ exchanger
Action of the SNS on the heart
release norepinephrine -interacts with adrenergic receptors on cell membrane of myocytes Causes: 1) Inotropy 2) Chronotropy 3) Lusitropy
Inotropy
Contractility or the ability of the heart to develop force at a given muscle fiber length (assuming hr is constant and volume of ventricles at end of diastole is constant)
Chronotropy
Increase in speed of cardiac contraction
Lusitropy
Acceleration of cardiac relaxation
Chronotropy cause
- norepinephrine and epinephrinne are released from SNS
- act on B1-receptor on cardiac pacemaker cells (SA node)
- B-adrenergic stimulation changes the ionic properties within the cells so they spontaneously initiate APs faster (increasing heart rate)
Parasympathetic effect on chronotopy
Acetylcholine binds to muscarinic receptors and reduced the spontaneous rate at whih APs are generated in the SA node
Positive inotrope
Change in inotropy due to administration of a drug
MOA of positive inotropes
1) many activate B-adrenergic receptors
2) activates series of secondary messengers within the cardiac myocytes
3) Protein kinase A -induced phosphorylation of specific membrane proteins –> incuding phospholamban and L-type Ca2+ channels
4) Phosphorylated phospholamban acts on SR (a SE membrane protein) -facilitates reuptake of Ca2+ by SR
5) Increase in the amount of ca2+ available for cross-bridge cycling
6) more forceful contraction
Lusitropy MOA
- the result of activation of phospholamban
- this enhances Ca2+ reuptake into the SR after contraction
- thereby facilitating its removal from the contractile filaments and preparing for next contraction
