The TRPM7 ion channel functions in cholinergic synaptic vesicles and affects transmitter release.
A longstanding hypothesis is that ion channels are present in the membranes of synaptic vesicles and might affect neurotransmitter release. Here we demonstrate that TRPM7, a member of the transient receptor potential (TRP) ion channel family, resides in the membrane of synaptic vesicles of sympathetic neurons, forms molecular complexes with the synaptic vesicle proteins synapsin I and synaptotagmin I, and directly interacts with synaptic vesicular snapin. In sympathetic neurons, changes in TRPM7 levels and channel activity alter acetylcholine release, as measured by EPSP amplitudes and decay times in postsynaptic neurons. TRPM7 affects EPSP quantal size, an intrinsic property of synaptic vesicle release. Targeted peptide interference of TRPM7's interaction with snapin affects the amplitudes and kinetics of postsynaptic EPSPs. Thus, vesicular TRPM7 channel activity is critical to neurotransmitter release in sympathetic neurons.
Krapivinsky
Grigory
G
Howard Hughes Medical Institute, Cardiology, Children's Hospital Boston, 1309 Enders Building, 320 Longwood Avenue, Boston, MA, USA.
Mochida
Sumiko
S
Krapivinsky
Luba
L
Cibulsky
Susan M
SM
Clapham
David E
DE
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D016253:Microscopy, Immunoelectron / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017783:Superior Cervical Ganglion / Q000166:cytology; D013569:Synapses / Q000145:classification / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology* / Q000648:ultrastructure; D050053:TRPM Cation Channels / Q000737:chemistry / Q000502:physiology*; D014162:Transfection / Q000379:methods; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C498452:Snapin protein, rat; D050053:TRPM Cation Channels; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; C486584:Trpm7 protein, rat; D000109:Acetylcholine