Ch. 5 Synaptic transmissionElectrical synapse Chemical synapse

雙向快速

Electrical synapse: to synchronize electrical activity among populations of neurons (hypothalamus)

ATP, c-AMP

crayfish 小龍蝦

Chemical synapse

AP

voltage-dependentCa2+ channels

Quantal transmission at neuromuscular synapses

• End plate potential (EPP)

• spontaneous changes occur in muscle cell mambrane miniature end plate potentials (MEPPs): occur even in the absence of stimulation, block by curare (ACh receptor blocker)

• EPP = summation of MEPPsLow Ca2+

EPP fluctuations

• 假說： these “quantal” fluctuations suggest that EPPs are made up of individual units, each equivalent to a MEPP

• 驗證： independent occurrence of unitary events (Poisson statistics): predict the distribution of EPP amplitudes

• 結論： presynaptic AP causes a postsynaptic EPP because it synchronizes the release of many transmitter quanta

Release of transmitters from synaptic vesicles: one synaptic vesicle is one MEPP

Fusion of synaptic vesicles with the presynaptic membrane 4-AP 會影響 AP 的 duration-> Ca2+

Dock: two membranes become tightly associated with each other

prime: active fusion of the membranes

The role of Ca2+ in transmitter secretion

• 有五種實驗證明 nerve terminal 有 voltage dependent Ca2+ channels 存在： (1) Na+ channels blocker (2) voltage clamp experiment 如圖所示 (3) Ca2+ imaging 如下圖 (4) 直接打入 Ca2+ (5) Ca2+ chelators

• The purpose of AP is to activate Ca2+ channels

-latrotoxin triggers Ca2+ independent exocytosis

Block Na+ & K+ channels

Ca2+ channel blocker鎘

Fura-2

Ca2+ chelators

在 presynaptic neuron 打入 Ca2+

Synaptotagmin:Ca2+ sensor, bind to neurexins

NSF & SNAP:common proteins in fusion, 與SNARE 結合 (SNAP receptors 包括 synaptobrevin, syntaxin& SNAP-25)

Toxins that affect transmitter release

• Clostridial toxins ( 梭狀芽孢桿菌毒素 ), botulism ( 肉類桿菌中毒 ), tetanus ( 破傷風 )

• botulinum toxin & tetanus toxin: cleave synaptobrevin, syntaxin & SNAP-25

• female black widow spider: -latrotoxin triggers Ca2+-independent exocytosis, bind to neurexins

Ch. 6 Neurotransmitters

• The utility cycle of all neurotransmitters: (1) synthesized & packaged (2) release & binding (3) removed or degraded

• classified into tow broad categories: (1) small-molecule NMs (2) neuropeptide

• 1926, Otto Loewi

What defines a neurotransmitter?

Vagus nerve

Heart rate

Heart rate

“vagus substance” ACh

Criteria that define a substance as a neurotransmitter: Box A 斜體字

The comparisons of neurotransmitters to hormones

Action at a distancevasopressin, oxytocin, can be as a hormone and as a NM

Two major categories of neuro-transmitters

(1)small-moleculeneurotransmitters: ATP, AMP

(2) peptideneurotransmitters

請任舉兩個實驗證明 nevre terminal 具有 voltage-dependent Ca2+ channels 。

請說明 Otto Loewi 證明神經傳導物質存在的實驗。