1

Wang Haitao

2

Research area:Voltage-gated Na channels are responsible for initiation of electrical signaling in nerve, muscle and other excitable cells, and voltage-gated Ca channels are responsible for initiation of synaptic transmission in neurons, excitation-contraction in muscle, secretion in endocrine cells, and many other processes.

3

Ca++ palys important role in trigger presynaptic transmitter release

4

CaM-binding domain (CBD)CaS dependent inactivation

IQ-like motif(IM)CaS ( Ca sensor)dependent faciliation

Ca2.1, (P/Q type Ca channel)

5

Methods

• Cultured SCG(superior cervical ganglion )neuron form fast cholinergic synaptic transmission between them cDNAs transfection to exogenous express WT or Mutant P/Q

type Calcium channels in SCG

• Whole cell recording

• Sharp electrode intracellular reocording

6

P/Q-Type Ca2+ Currents in SCG Neurons

7

Calcium Dependent Facilitation and Inactivation of CaV2.1 Channels

EPSP = k*(ICa)n

k = 1 ,n = 3.5

8

PPF and PPD Mediated by CaV2.1 Channels

9

PPF and PPD Mediated by CaV2.1 Channels

10

Plasticity of Synaptic Transmission Mediated by CaV2.1 Channels during Bursts of Neuronal Activity

11

Augmentation and PTP Mediated by CaV2.1 Channels

Summary• A mutation of the Iq-like motif in the C terminus that blocks

Ca2+/CaS dependent facilitation of the P/Q-type Ca2+ current markedly reduces facilitation of synaptic transmission.

• Deletion of the nearby calmodulin-binding domain,which inhibits CaS-dependent inactivation,substantially reduces depression of synaptic transmission.

• Residual Ca2+ in presynaptic terminals can act through CaS dependent regulation of CaV2.1 channels to induce short-term synaptic facilitation and rapid synaptic depression. Activity-dependent regulation of presynaptic CaV2.1 channels by CaS proteins may therefore be a primary determinant of short-term synaptic plasticity and information-processing

12