Postsynaptic mechanisms underlying responsiveness of amygdaloid neurons to cholecystokinin are mediated by a transient receptor potential-like current.
Projection neurons of mouse basolateral amygdala responded to CCK with an inward current at a holding potential of -70 mV. This response was mediated by CCK2 receptors as indicated by agonist and antagonist effectiveness, and conveyed via G-proteins of the G(q/11) family as it was abolished in gene knockout mice. Maximal current amplitude was insensitive to extracellular potassium, cesium, and calcium ions, respectively, whereas amplitude and reversal potential critically depended upon extracellular sodium concentration. The current reversed near -20 mV consistent with activation of a mixed cationic channel reminiscent of transient receptor potential (TRP) channels. Extracellular application of the non-selective TRP channel blockers 2-APB, flufenamic acid, Gd3+, and ruthenium red, respectively, inhibited CCK induced inward currents. Single cell PCR confirmed the expression of TRPC1,4,5 and coexpression of TRPC1 with TRPC4 or TRPC5 in some cells. CCK responses were associated with depolarization leading to an increase in cell excitability.
Meis
Susanne
S
Institut für Physiologie, Medizinische Fakultät, Otto-von-Guericke-Universität, Leipziger Str. 44, D-39120 Magdeburg, Germany. susanne.meis@medizin.uni-magdeburg.de
Munsch
Thomas
T
Sosulina
Ludmila
L
Pape
Hans-Christian
HC
D000200:Action Potentials / Q000187:drug effects; D000679:Amygdala / Q000166:cytology*; D000818:Animals; D000831:Animals, Newborn; D002766:Cholecystokinin / Q000494:pharmacology*; D004347:Drug Interactions; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000172:deficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013569:Synapses / Q000187:drug effects*; D050051:Transient Receptor Potential Channels / Q000502:physiology*
D044385:GTP-Binding Protein alpha Subunits; D012333:RNA, Messenger; D050051:Transient Receptor Potential Channels; D002766:Cholecystokinin