cardiovascular system - electrical activity of heart Flashcards
role of ion channels
-bring in various ions to change the electrical activity of the heart
-control level of Ca2+ and other ions
excitable cells (able to generate their own electrical activity)
-myocytes
-skeletal muscle
-nerves
diads
-where T-tubule is connected/coupled to the sarcoplasmic reticulum
L-type Ca2+ channel
-sits on T-tubule
-in close proximity to ryanodine receptor
ryanodine receptors (RyR)
-part of sarcoplasmic reticulum that stores Ca2+
calcium-induced calcium release
(C-I-C-R)
-ions come in from outside through the L-type Ca2+ channel
-RyR senses Ca2+ influx causing Ca2+ release from SR
-Ca2+ required to come in from outside which induces a much larger release from the internal store (SR)
percentage of Ca2+ required for contraction
-approx. 75% of Ca2+ from internal structures (sarcoplasmic reticulum)
-approx. 25% comes from extracellular space (through L-type Ca2+ channels)
Ca2+ conc. in cell
-when completely relaxed: ~0.1µM
-when contracting: ~10µM
excitation-contraction coupling (brief overview)
-Ca2+ enters cell through L-type Ca2+ channel
-CICR occurs
-Ca2+ interacts with troponin-C, causing troponin-I to uncover myosin binding site on actin
-intracellular Ca2+ reabsorbed or removed by respective mechanisms
-as intracellular Ca2+ decreases, Ca2+ dissociates from troponin-C
-myosin binding site on actin is inhibited
-ATP required to remove myosin from actin and reset sarcomere to normal length
Ca2+ removed from cell
-ATP-dependent Ca2+ pump
-Na+/Ca2+ exchanger (and Na+/K+ pump to prevent Na+ overload)
Ca2+ reabsorbed into sarcoplasmic reticulum (SR)
-sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pump (also ATP dependent)
calcium and force production
-Ca2+ binds to troponin-C (TN-C) on actin thin filament
-troponin-I (TN-I) exposes site on actin so it is available for myosin head to bind
-ATP hydrolysis supplies energy for actin-myosin conformational change
-‘ratcheting’ of actin-myosin and shortening of sarcomere occurs
-Ca2+ dissociates from TN-C and myosin unbinds from actin with energy from ATP
phospholamban and SR calcium uptake
-SR reabsorbs Ca2+ via SERCA
-disinhibition of phospholamban increases rate of Ca2+ uptake
-cytosolic Ca2+ decreases, Ca2+ removed from TN-C
-excess Ca2+ removed from cell by other processes
phospholamban
-a protein that inhibits the activity of SERCA
-allows rate of relaxation to be regulated
-can be phosphorylated to dissociate the interaction between itself and SERCA
inhibiting/slowing down relaxation
-allow phospholamban and SERCA to interact
-slows down activity of SERCA as the rate at which Ca2+ is removed is slowed