M-type K+ currents in rat cultured thoracolumbar sympathetic neurones and their role in uracil nucleotide-evoked noradrenaline release

1 Cultured sympathetic neurones are depolarized and release noradrenaline i n response to extracellular ATP, UDP and UTP. We examined the possibility t hat, in neurones cultured from rat thoracolumbar sympathetic ganglia, inhib ition of the M-type potassium current might underlie the effects of UDP and UTP. 2 Reverse transcriptase-polymerase chain reaction indicated that the cultur ed cells contained mRNA for P2Y(2)-, P2Y(4)- and P2Y(6)-receptors as well a s for the KCNQ2- and KCNQ3-subunits which have been suggested to assemble i nto M-channels. 3 In cultures of neurones taken from newborn as well as from 10 day-old rat s, oxotremorine, the M-channel blocker Ba2+ and UDP all released previously stored [H-3]-noradrenaline, 4 The neurones possessed M-currents, the kinetic properties of which were s imilar in neurones from newborn and 9-12 day-old rats. 5 UDP, UTP and ATP had no effect on M-currents in neurones prepared from ne wborn rats. Oxotremorine and Ba2+ substantially inhibited the current. 6 ATP also had no effect on the M-current in neurones prepared from 9-12 da y-old rats. Oxotremorine and Ba2+ again caused marked inhibition. In contra st to cultures from newborn animals, UDP and UTP attenuated the M-current i n neurones from 9-12 day-old rats; however, the maximal inhibition was less than 30%. 7 The results indicate that inhibition of the M-current is not involved in uracil nucleotide-induced transmitter release from rat cultured sympathetic neurones during early development. M-current inhibition may contribute to release at later stages, but only to a minor extent. The mechanism leading to noradrenaline release by UDP and UTP remains unknown.