Albert von Szent-Gy

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• Albert von Szent-Györgyi Nagyrapolt
  (A.?????,????)????????, ?1937???????????("for
  his discoveries in connection with the biological
  combustion processes, with special reference to
  vitamin C and the catalysis of fumaric acid)
• ???????40
• ???????,??????????

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• ??? ??-???????????
• ??????????,?????????
• ????????????(acetylcholine, Ach)
• ??????????(quantal release)
• ??-?????(????-???)???
• ????AP?Ach????????AP

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SIR BERNARD KATZ (Great Britain)
Ulf von Euler (Sweden)
Julius Axelrod (USA)
1970 Nobel Laureate in Physiology or
Medicine "for their discoveries concerning the
humoral transmittors in the nerve terminals and
the mechanism for their storage, release and
inactivation"
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Sir Bernard Katzs Work
His research uncovered fundamental properties of
synapses, the junctions across which nerve cells
signal to each other and to other types of cells.
By the 1950s, he was studying the biochemistry
and action of acetylcholine, a signalling
molecule with which synapses linking "motor
nerves" to muscles stimulate contraction. Katz
won the Nobel for his discovery that
neurotransmitter release at synapses is
"quantal"--that is, that at any particular
synapse the amount of neurotransmitter released
is never less than a certain amount, and if more
is always an integral number times this amount.
This circumstance arises, scientists now know,
because, prior to their release into the synaptic
gap, transmitter molecules reside in like-sized
subcellular packages known as synaptic vesicles
(more at exocytosis).
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Julius Axelrods Work
Axelrod received his Nobel Prize for his work on
the release, reuptake and storage of the
neurotransmitters epinephrine and norepinephrine,
also known as adrenaline and noradrenaline.
Working on monoamine oxidase (MAO) inhibitors in
1957, Axelrod showed that catecholamine
neurotransmitters do not merely stop working
after they are released into the synapse.
Instead, neurotransmitters are recaptured
(reuptaken) by the pre-synaptic nerve ending, and
recycled for later transmissions. He theorized
that epinephrine is held in tissues in an
inactive form and is liberated by the nervous
system when needed. This research laid the
groundwork for later selective serotonin reuptake
inhibitors (SSRIs), such as Prozac, which block
the reuptake of another neurotransmitter,
serotonin.
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?????????????----???????????
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Henry Hallett Dale (Great Britain)
Otto Loewi (Germany)
1936 Nobel Laureate in Physiology or Medicine
"for their discoveries relating to chemical
transmission of nerve impulses"
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Dales contribution
During the 1940s Dale was embroiled in the
scientific debate over the nature of signaling at
the synapse. Dale and others believed that
signaling at the synapse was chemical, while John
Carew Eccles and others believed that the synapse
was electrical. It was later found that most
synaptic signalling is chemical, but there are
some synapses that are electrical. Dale also
originated the scheme used to differentiate
neurons according to what neurotransmitter they
release. Thus, neurons releasing norepinephrine
(a.k.a. noradrenaline) are called noradrenergic,
neurons releasing GABA are GABAergic, and so on.
This scheme is related to Dale's principle
(sometimes erroneously referred to as Dale's
Law). This principle states that each neuron
releases only one type of neurotransmitter.
Dale's principle has been shown to be false many
neurons release neuropeptides in addition to
amino acids or amines (Bear, et al. 2001).
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• ????????Ach????????????
• Ach
• ?
• ?????N2?ACH??
• ?
• Na?K???Ca2????
• ?
• ????(endplate potential)
• (????????)
• ?
• ????????????

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• ???????Ach?????(quantal release)
• (Kats)
• ?Ach?????(?10000?Ach??)
• Ach????????????
• ????(endplate potential, EPP)
  ????????,??Ach????????????????,????50mV,??????????
  ???3-4?,?????????11??????
• ?????(miniature endplate potential,
  MEPP)??Ach??????????????(????????,?????1?,????0.4
  mV,???Ach??????)?

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• ????????Ach?????????Ca2??
• ?Ach?????(?10000?Ach??)
• Ach????????????
• ????(endplate potential, EPP)
  ????????,??Ach????????????????,????50
  mV,?????????????3-4?,?????????11??????
• ?????(miniature endplate potential,
  MEPP)??Ach??????????????(????????,?????1?,????0.4
  mV,???Ach??????)?

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• ?????????Ach?????????????
• Ach??????????????????

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• Ach??????-????????
• ???? ??(0.2 sec)?????Ach
• ?????????????Ach???????
• ?Ach??????,??????????
• ????????????????

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• ??? ?????????
• ?????????????????
• (?) ??(sarcomere,?????)
• ???????????,???????1.5-3.5?m,
• ???2.0-2.2?m?
• 1. ????(myofibril)
• ? 1-2?m, ?????? ?,???????????????,???
  ????????????????????????????(1.5
  ?m)?????????????????

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?????,??? M?????????? Z??????????
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• 2. ????
• ????(T?)???????,?Z?????????????????,???????,????
  ???,?????????????????????
• ????(L?,???)????????,???????????,???????,???????
  ????,????

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• ????????Ca2??
• ?????(LSR)?????????,??
• ??
• ?????(junctional SR)???(terminal
  cisterna)???Ca2????,?????????(calsequestrin)???
  ?????(ryanodine??)?

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???(triad)?? ??????????????,????12nm???????
??????????????????
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• ??????????????
• (excitation-contraction coupling)
• ??????????????????????
• ????????
• 1. ????AP??????????
• 2. ??AP?????Ca2????,Ca2??
• 3. ??Ca2??????????,??????

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• ??????????????Ca2???
• 1)???????
• 2)?? Ca2???Ca2???
• ??????Ca2????????

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????????????Ca2???????
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• ????????????????
• 50????Huxley??????(sliding theory)
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• ???????????
• ???????
• 1. ???????????,??????
• 2. ????H???,????????????
• ???,?????????,???????
• ????

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• ???????(????,myosin)
• ?? ????(????,actin)
• ???????? (tropomyosin)
• ???? (troponin)
• ?????????????????????
• ??????
• ?????Ca2??,???????Ca2??
• ?,???????????

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• ??????
• ?????????????????
• ?
• ????????Ca2
• ?
• Ca2???????
• ?
• ???????,???
• ?
• ??????(??)???????
• ?
• ????ATP??,????M?????,?????

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• ?????Ca2?????????
• (?)Ryanodine???Ca2??
• Ryanodine??Ca2????,?L??????????
• ????????Ca2????????L??????
• ???????SR??Ca2??????
• ?????????Ca2????????L??????
• ???????(Ca2-induced Ca2 release)??SR??
• Ca2?????

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• (?)???????Ca2???????
• ???(Ca2???)
• 1. SR????2 Ca2/ATP (100)
• 2. ????????????????
• ??(?Ca2??)
• 1. SR???????(70)
• 2. ????????(2)
• 3. Na-Ca2 ???(28)

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??
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• ?????????????????
• ???? ?? ? ????
• ??? (preload)????????????
• ????????????????????
• ??,?????????????
• ??? (afterload)????????????

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• ???? (isometric contraction)???????????,??????
• ???? (isotonic contraction)?????(?????????)????
  ??,??????
• ??? (single twich) ????????,?????????????

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• ???? (??????)?????????????,????????,???????????
  ??????,????????? (incomplete tetanus)????????,???
  ??????????????,???????? (complete
  tetanus)?????????????????

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• (?)?????????????????
• ??- ????
• 1. ??????????????????,???????????
• 2. ???????????????????????-?????
• 3. ??????(??- ????)??? ????,??????????????
  ??????????

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• (?)?????????????????
• ??- ????
• ??1???(????)????????
• ??2???(????)????????
• ?????????,?????????????,????,????????????,??????
  ,???????

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• (?)?????????????????
• ???????????
• ???
• ???
• ??????(contractility) ???????????,???????????

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• (?)?????????????
• ????(motor unit)???????????????????????
• ????(size principle)??????,?????????????????
• ???????????????
• ????????????????
• ??????????????

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• ??? ?????????
• ?. ?????????????
• ??????,???????????
• ????????????????????
• ?????????????????
• ???????
• ??????????,??????

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• ????????(101-151)
• ?????????
• ?????????
• ??????????
• ??????????????
• Cajal???????????????????

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?????????????????Ca2???? 1. ?????????????Ca2???
CICR 2. ?????????????Ca2??? AP 3.
?????G???????PLC? IP3 ? IP3-R ? ??
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• (?)??????????
• 1.??????(multi-unit smooth muscle)
• ????????,?????
• ???????
• ????????????(?)???????
• ???.

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• 2. ???????(single-unit smooth muscle)
• ???????(visceral smooth muscle)
• ????????????????,????
• ??????
• ?????????????????
• 3. ??????

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• (?)????????????
• ?????????????????????
• ??,?????????????????
• ????????????
• ????????????(varicosity)
• ?????????-55 -60mV
• ?????????????????

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