Klabunde 1 Flashcards
Resting membrane ventricular myocyte ______: Resting membrane potential (Em) is determined by:
-90mV concentrations of +/- ions across the cell membrane electric gradient relative permeability of cell membrane to ions ionic pumps
What main pump maintains ionic gradient:
What main pump maintains ionic gradient: Electrogenic : 3 Na out for every 2 K in, creating the negative potential w/in the cell
Cardiac tissue hypoxia and cardiac glycosides (ie: digoxin) do what to Na-K-ATPase pumps, causing RMP to become ______:
inhibited Na-K-ATPase RMP is more positive (partially depolarized)
Phase 0 Phase 1 Phase 2 Phase 3 Phase 4
Phase 0 Depolarization – Fast Na Phase 1 Transient outward K Phase 2 Plateau – L-type Ca Phase 3 Delayed rectif. Ikr (K in or out?) OUT Phase 4 Inward rectif. Ikr (K in)
Refractory period Effective (absolute) refractory period phases: Why? Relative refractory period
During phase 0, 1, 2, and part of 3, that cell is unexcitable h-gates are still closed At the end of ERP (end of phase 3) Suprathreshhold depolarization required to stimulate AP Not all the Na channels have recovered to resting state based on Em When activated: decreased phase 0 slope and lower amplitude
Phase 0 Phase 3 Phase 4
L-type Ca Delayed rectif. K If funny channels
Non-nodal cell RMP determined by:
K concentrations (slow leak out) K electric gradient (K+ drawn to –ve intracell.) relatively permeability memb. to K (not Na+ or Ca++) ionic pumps (NA/K ATPase, delayed Ikr)
RMP nodal cell Threshold
-64 -40
RMP non-nodal: Threshold potential ______: Depolarizes to ______mV:
-90 -70mV +30mV
Norepi binds to ____ receptor: B1 coupled to ____: stimulatory G protein (Gs): Gs activates _____ second messenger: cAMP act via:
B1 stimulatory G protein (Gs): adenylates cyclate increasing cAMP
- increases slow Na “pacemaker current” If “funny current”
- earlier opening of L-type Ca (phase 4)
- Shorter repolarization is also shortened
AcH binds to ____ receptor: M2 coupled to ____: Gi inhibits _____ second messenger: Decreased cAMP act via:
M2 inhibitory G protein (Gi): adenylates cyclate decreasing cAMP
- inhibiting slow Na “pacemaker current” If “funny current”
- Activates KAcH channels which hyperpolarize cells
…. So we went from nodal vs non-nodal AP (phases), RMP, threshold potential, and regulation (ANS and SNS) how does AP conduct cell-to-cell: how does this differ from vascuar myocytes: how does this AP result in the heart contracting
gap junctions located at intercalated discs syncytium
- non-conducting connective tissue separates/stalls AP
- slows conduction to 0.05m/s allows atrial contraction
Arrhythmias are generated via 3 mechanisms:
Abnormal automaticity
Triggered activity (EAD, DAD)
Reentry – conduction pathway prematurely stimulated by prev.AP
Abnormal automaticity, Effects which phase of AP:
phase 0 i.e. blocked by drugs (digitalis) i.e. inactivated by depolarization secondary to hypoxia Depresses slope, “fast response” converted to “slow response”
- Triggered activity EAD (early afterdepolarization) end of phase ____: DAD (delayed afterdepolarization) end phase ____:
Phase 3 – Na channels still blocked, Ca++ carries depolarizing current
Phase 3/start phase 4 – elevations in intracellular Ca++ secondary to ischemia or excess catecholamines
Klabunde 3:
Structure myocyte vs smooth m
Excitation-contraction coupling myocyte vs smooth m
More second messengers
Draw a single sarcomere and label 4 parts: Draw a tropomysosin complex (myosin, actin, tropomyosn and Tn-T/I/C): Draw a tropomyosin complex w. (myosin, actin, tropomyosin and Tn-T/I/C):
Basic contractile unit Consists of 4 components:
Sarcomere actin (thin filament) myosin (thick filament) titin tropomyosin/tropomyosin complex
Sarcomere turns into: ___ turns into: ____ turns into: myocytes with ____ discs
myofilament turns into: myofibril turns into: myocytes with intercalated discs
Excitation-contraction coupling myocyte vs smooth m Describe the 5 key steps: 1.
- L-type channel is what type of channel and what phase:
3.
4.
5.
- AP travels down T-tubule
- Voltage-sensitive dihydropyridine receptors (L-type calcium channels) open to permit calcium entry during phase ____ (phase 2)
- Ca influx triggers a subsequent release of Ca stored in SR through calcium-release channels: “ryanodine receptors”
4 Ca binds to TN-C conformational change, exposes a site on actin, binds myosin ATPase on myosin head, ATP hydrolysis that supplies energy “ratcheting” actin and myosin filaments slide/shorten, ATP hydrolysis for Ca release end of phase 2
- calcium entry into the cell slows and calcium is sequestered by the SR by an ATP-dependent calcium pump (SERCA, sarco-endoplasmic reticulum calcium-ATPase)
describe ratcheting and sliding-filament theroy
-Ca binds to TN-C attached to tropomyosin -conformational change, exposes a site on actin, binds myosin ATPase on myosin head -ATP hydrolysis that supplies energy “ratcheting” actin and myosin filaments slide/shorten -ATP hydrolysis for Ca release end of phase 2 -continues to ratchet as long as Ca concentration is high
PDE3i MoA: cardiac myocyte: vascular smooth m.:
PDE3i prevents degradation of PDE3 increasing cAMP (similar to B2 stimulation)
Cardiac myocyte: = increased cAMP = increased PKA (RyR > release Ca++, phosphorylates phospholamban = > SR SERCA uptake, enhances Ca++ binding to TN-C)
Vascular smooth m.: = increased cAMP = decreased MLCK (myosin light chain kinase) = smooth muscle relaxation
RyR release NE Gs vs Gq:
Gs - cAMP - PKA
Gq - IP3 - PIP2 = > Ca++ release
Lusitropy what enhances lusitropy:
< Ca++ allows relaxation -permiting troponin-tropomyosin to resume resting conformation
phosphorylation of phospholamban - enhanced SERCA channel ischemia = Ca overload - impaired relaxation
Smooth muscle cells: invaginations called ____, rather than T-tubules: actin and myosin form ____, rather than z-lines: connected by:
calveolae - >SA dense bodies gap junctions
smooth m AP vs. cardiac myocyte AP:
partially contracted state b/c of adrenergic tone
- AP, Ca enters via L-type
- Ca released SR
- Ca + CALMODULIN activate MLCK
- MLCK + ATP phosphorylates myosin = contraction
CALMODULIN:
MLCK
MoA cAMP on MLCK
Ca + CALMODULIN activate MLCK
MLCK + ATP phosphorylates myosin = contraction
inhibits MLCK .:. causes relaxation
smooth m.:
Gq binds:
causes:
Gs:
causes:
NO does what:
Gq - NE, AII, ET-1,
Gq - IP-3 - protein kinase C -
>Ca CONTRACTION
Gs - NE, adenosine, PGI2
Gs - cAMP - Decreases MLCK = VASODILATION
NO - > cGMP - Decreases MLCK = VASODILATION
NO MoA vasodilation:
ET-1 MoA vasoconstriction:
cGMP - inhib MLCK = vasodilate
Gq PIP2 - IP3 PK-C - >Ca = vasoconstrict
Wigger’s diagram:
Phase 1:
Atrial systole: A-V Valves Open; Semilunar Valves Closed
Phase 2 -
Phase 3 -
Phase 4 -
Phase 5 -
Phase 6 -
Phase 7 -
Isovolumetric Contraction
Rapid Ejection
Reduced Ejection
Isovolumetric Relaxation
Rapid Filling
Reduced Filling
Draw wigger’s diagram
CO - what is more imortant HR or SV?
HR - can increase CO 100-200%
SV increase <50%
