Q_f = k[(P_c-P_i) - σ(π_c - π_i)]

Filtration: NDF > 0

Reabsorption: NDF < 0

(flux includes the filtration constant "k," NDF does not)

Smooth muscle contraction

(not everything, just the parts that need some cobweb-clearing)

Actin & myosin interact according to the sliding filament mechanism

Ca⁺⁺ interacts with calmodulin and myosin light chain kinase (MLCK) to activate myosin

1. Depolarization opens Ca⁺⁺channels, Ca⁺⁺ flows into cell down its electrochemical graident, increasing intracellular [Ca⁺⁺]

2. Hormones & NT release Ca⁺⁺ from the SR through IP₃-gated Ca⁺⁺ channels

3. Intracellular [Ca⁺⁺] increases

4. Ca⁺⁺-calmodulin --> activates MLCK --> phosphorylates myosin, myosin binds to actin --> CONTRACTION

5. A d/c in intracellular [Ca⁺⁺] --> inactivation of MLCK --> myosin phosphatase dephosphorylates MLCK --> RELAXATION

Latch state - MLCK is dephosphorylated when myosin is attached to actin & cannot detach

MLCK can be dephosphorylated by phosphate at any time in the cycle

What causes smooth muscle to contract?

To relax?

Molecular basis for contraction:

  Ca⁺⁺-calmodulin

  activation of MLCK

NT/hormones:

NE, epi       a-1/IP3                   contract

                 B-2/cAMP                relax

ACh            muscarinic receptor  contract

                 indirect via NO         relax

Angiotensin II   AT-II/IP3           contract

Vasopressin      VP rec/IP3              contract

Endothelin        ET rec/IP3               contract

Adenosine   adenosine rec/cAMP  relax

1. Action potentials intitiate depolarization of T-tubules

2. Depolarization of T tubules --> opens Ca⁺⁺ release channels in SR --> release of Ca⁺⁺

3. Intracellular [Ca⁺⁺] increases

4. Ca⁺⁺ binds troponin C on the thin filaments --> tropomyosin moved out of the way, cross-bridge cycling begins

  a. no ATP is bound to myosin, myosin is attached to actin (if no ATP --> rigor)

  b. ATP binds to myosin, myosin is released from actin

  c. myosin is displaced toward the plus end of actin

  d. myosin attaches to a new site on actin (power-generating stroke), ADP released, returning myosin to rigor state

  e. cycle repeats as long as Ca⁺⁺ is bound to troponin C

5. When SERCA reaccumulates Ca⁺⁺ --> relaxation

Isometric - length held constant, preload is fixed, there is NO shortening

Isotonic - load held constant, afterload is fixed, shortening is measured

Length-tension relationship: measures tension developed during isometric contractions

  - passive tension: developed by stretching muscle to different lengths

  - total tension: developed when muscle is stimulated to contract at different length

  - active tension: the difference between passive & total; proportional to # of cross-bridges formed; will be maximum when there's max overlap of thick and thin filaments

Force-velocity relationship: measures the velocity of shortening of isotonic contractions when muscle is challenged with different afterloads

  - velocity decreases as afterload increases