Signaling across chemical synapes/neuromuscular transmission/E-C coupling/crossbridge cycling

first step of signaling across chemical synapses

action potential in bouton generated y opening of Na+ channels

second step of signaling across chemical synapses

depolarization opens ca2+ channels

third step of signaling across chemical synapses

ca2+ elevation occurs in microdomain and binds to synaptotagmin causing opening of fusion to pore

fourth step of signaling across chemical synapses

neurotransmitter passes through fusion pore and diffuses into the cleft

first step of neuromuscular transmission

action potential conduction down the motor nerve

second step of neuromuscular transmission

opening of voltage gated Ca2+ channel and ca2+ influx

third step of neuromuscular transmission

vesicle exocytosis and ACh release

fourth step of neuromuscular transmission

ACh diffusion and binding to nAChR

fifth step of neuromuscular transmission

nAChR opening and membrane depolarization (endplate potential)

sixth step of neuromuscular transmission

spreading of endplate potential

seventh step of neuromuscular transmission

opening of voltage-gated Na+ channel

eighth step of neuromuscular transmission

action potential generation and conduction down the sarcolemma

ninth step of neuromuscular transmission

ACh degradation by AChE

four mechanistic components of skeletal muscle contraction

synaptic transmission at NMJ, action potential generation & conduction, Ca2+ release from SR, tension development/cross bridge cycling

information flow during E-C coupling step 1

an action potential is propagated over the entire muscle surface

information flow during E-C coupling step 2

action potential reaches down the t-tubule membrane into the interior of the muscle fiber

information flow during E-C coupling step 3

voltage gated Ca2+ channels in t-tubule membrane sense the depolarization

information flow during E-C coupling step 4

VGCC activation signals RyR in the SR membrane to release Ca2+ into sarcoplasm leading to muscle contraction

Troponin C

binds Ca2+ ions, providing the key link between the Ca2+ release from SR an dthe muscle contraction

Troponin T

contacts tropomyosin in the actin groove

Troponin I

contacts tropomyosin in the actin groove, playing a role in the myosin head binding site

first step in cross bridge cycling

energized: atp split by myosin ATPase ; ADP and Pi remain attached to myosin; energy stored i cross bridge (energy cocks cross bridge)

second step in cross bridge cycling when there is no Ca2+ present

resting: no excitation; no Ca2+ released; actin and myosin prevented from binding; no cross-bridge; muscle fiber remains at rest

second step in cross bridge cycling when there is Ca2+ present

binding: Ca2+ released on excitation; removes inhibitory influence from actin, enabling it to bind with cross bridge

third step in cross bridge cycling

bending: power stroke of cross bridge triggered on contact between myosin and actin: Pi release during and ADP released after power stroke

fourth step of cross bridge cycling

detachment: linkage between actin and myosin broken as fresh molecule of ATP binds to myosin cross bridge; cross bridge assumes original conformation; ATP hydrolyzed (cycle starts again at step 1)

G-protein interaction with GPCRs step 1

weak interaction between GPCR and G_alpha-GDP

G-protein interaction with GPCRs step 2

agonist binds to GPCR

G-protein interaction with GPCRs step 3

GPCR activates (strong interaction between GPCR and G_alpha-GDP)

G-protein interaction with GPCRs step 4

GDP-GTP exchange in G_alpha

G-protein interaction with GPCRs step 5

G_alpha - GTP dissociates

G-protein interaction with GPCRs step 6

ROS exchanges GTP/GDP on G_alpha, agonist dissociates from GPCR, GPCR-agonist complex gets internalized