Mechano- and chemosensitivity of rat nodose neurones--selective excitatory effects of prostacyclin.
Nodose ganglion sensory neurones exert a significant reflex autonomic influence. We contrasted their mechanosensitivity, excitability and chemosensitivity in response to the stable prostacyclin (PGI2) analogue carbacyclin (cPGI) in culture. Under current clamp conditions we measured changes in membrane potential (DeltamV) and action potential (AP) responses to mechanically induced depolarizations and depolarizing current injections before and after superfusion of cPGI (1 microM and 10 microM). Chemosensitivity was indicated by augmentation of AP firing frequency and increased maximum gain of AP frequency (max. dAP/dDeltamV), during superfusion with cPGI. Results indicate that two groups of neurones, A and B, are mechanosensitive (MS) and one group, C, is mechanoinsensitive (MI). Group A shows modest depolarization without AP generation during mechanical stimulation, and no increase in max. dAP/dDeltamV, despite a marked increase in electrical depolarization with cPGI. Group B shows pronounced mechanical depolarization accompanied by enhanced AP discharge with cPGI, and an increase in max. dAP/dDeltamV. Group C remains MI after cPGI but is more excitable and markedly chemosensitive (CS) with a pronounced enhancement of max. dAP/dDeltamV with cPGI. The effect of cPGI on ionic conductances indicates that it does not sensitize the mechanically gated depolarizing degenerin/epithelial Na+ channels (DEG/ENaC), but it inhibits two voltage-gated K+ currents, Maxi-K and M-current, causing enhanced AP firing frequency and depolarization, respectively. We conclude that MS nodose neurones may be unimodal MS or bimodal MS/CS, and that MI neurones are unimodal CS, and much more CS to cPGI than MS/CS neurones. We suggest that the known excitatory effect of PGI2 on baroreceptor and vagal afferent fibres is mediated by inhibition of voltage-gated K+ channels (Maxi-K and M-current) and not by an effect on mechanically gated DEG/ENaC channels.
Snitsarev
Vladislav
V
Cardiovascular Research Center, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Whiteis
Carol A
CA
Chapleau
Mark W
MW
Abboud
François M
FM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism; D011312:Pressure; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011465:Prostaglandins, Synthetic; C026678:carboprostacyclin; D011464:Epoprostenol