Evidence for a voltage-dependent enhancement of neurotransmitter release mediated via the synaptic protein interaction site of N-type Ca2+ channels.
Secretion of neurotransmitters is initiated by voltage-gated calcium influx through presynaptic, voltage-gated N-type calcium channels. These channels interact with the SNARE proteins, which are core components of the exocytosis process, via the synaptic protein interaction (synprint) site in the intracellular loop connecting domains II and III of their alpha1B subunit. Interruption of this interaction by competing synprint peptides inhibits fast, synchronous transmitter release. Here we identify a voltage-dependent, but calcium-independent, enhancement of transmitter release that is elicited by trains of action potentials in the presence of a hyperosmotic extracellular concentration of sucrose. This enhancement of transmitter release requires interaction of SNARE proteins with the synprint site. Our results provide evidence for a voltage-dependent signal that is transmitted by protein-protein interactions from the N-type calcium channel to the SNARE proteins and enhances neurotransmitter release by altering SNARE protein function.
Mochida
S
S
Department of Physiology, Tokyo Medical College, Tokyo 160, Japan.
Yokoyama
C T
CT
Kim
D K
DK
Itoh
K
K
Catterall
W A
WA
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005089:Exocytosis; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D050600:SNARE Proteins; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors; D033921:Vesicular Transport Proteins
D015220:Calcium Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010455:Peptides; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid