Exam 2 Lecture 6

Exam 2 Lecture 6 - Lecture 6 March 10, 2005 Correction for...

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Lecture 6 March 10, 2005 Correction for notes from Tuesday 3/8/05: the "base" of the heart refers to the upper, broader end of the heart CONTRACTILE PHYSIOLOGY OF THE HEART (with a focus on the left ventricle) Fig 14.13: Excitation-Contraction (EC) Coupling (also known as electromechanical coupling) Na+, K+, and Ca2+ have important roles in cardiac function No Ca2+ heart becomes acontractile (can't contract) No Na+ hear becomes inexcitable Modest changes in [K+] heart malfunction (e.g. a 2-3x increase in extracellular [K+] leads to cardiac arrest) This figure shows 2 cells, which can be either slow or fast response cells. An action potential in one cell crosses via a gap junction to the 2nd cell and induces a depolarization, which leads to contraction Steps Na+ ions flow across nexi (gap junction) wave of depolarization passes longitudinally along the sarcolemma and into the cell down T tubules (which are continuous with the sarcolemma) Voltage-dependent opening of L-type Ca2+ channels (these are the types of channels that we find in ventricles, the structure we're concentrating on) Ca2+ enters the cell in the resting state prior to depolarization down its concentration gradient. At rest, there is a 10,000x difference in [Ca2+] between the intra and extracellular fluids Inside the cell = 10-7 mols, or 1/10th of a micromole Outside the cell = 1 millimole Calcium induced calcium release: Ca2+ influx from L-type channels are not enough to cause contraction. Rather, these Ca2+ ions bind to Ca2+ receptors on the sarcoplasmic reticulum (SR) and sarcolemma/ T tubules, which opens these new Ca2+ channels release of stored Ca2+ from SR and T tubules into the cytosol This SR Ca2+ sufficiently raises the [cytoplasmic Ca2+] to induce contraction Protein Ca2+ receptors (named after the class of drugs that block them) Dihydropyradine receptors : L-type channels in the sarcolemma Ryanodine receptors : located in the SR Ca+ from the SR binds to troponin conformational change in troponin I (TNI, TI, or inhibitory troponin) , which usually covers a tropomyosin element that has myosin binding sites but the conformational change exposes those myosin binding sites crossbridge cycle sarcomere shortens generates force Research going on right now: a small amount of Ca2+ can be released from the SR in gradient fashion. There are dyes that release light when Ca2+ is released; these are called calcium sparks. Relaxation of the sarcomere occurs through 2 ways
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Ca2+-ATPases in the SR and sarcolemma extract Ca2+ and restore it in the SR or transport it back out of the cell Ca2+-Na+ exchangers (antiports) use energy from Na+ influx to pump Ca2+ out of the cell After relaxation, the cell is ready from another action potential Fig 14.18: EC Coupling leads to mechanical event EC process occurs several times a minute
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Exam 2 Lecture 6 - Lecture 6 March 10, 2005 Correction for...

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