Dual regulation of heat-activated K+ channel in rat DRG neurons via alpha(1) and beta adrenergic receptors.
OBJECTIVE
The present study aimed at understanding regulation of heat-activated K+ channels expressed in DRG neurons.


METHODS
Whole-cell patches were made from cultured rat dorsal root ganglion (DRG) neurons and heat-activated currents were monitored.


RESULTS
A temperature rise from 25 to 45 degrees C generated outward currents with the current/voltage relation revealing a reversal potential of approximately -90 mV, that are inhibited by the K+ channel blockers, Ba2+ and tetraethylammonium, indicating that heat activates K+ channels expressed in DRG neurons. Heat-activated K+ channel currents here was depressed by noradrenaline, and a similar effect was obtained with cirazoline, an agonist of alpha1 adrenergic receptors linked to G(q) protein involving PKC activation, and isoproterenol, an agonist of beta adrenergic receptors linked to G(s) protein involving PKA activation, but not UK14304, an agonist of alpha2 adrenergic receptors linked to G(i) protein. The noradrenaline action was prevented by GF109203X, a PKC inhibitor, or H-89, a PKA inhibitor, and a complete inhibition was obtained with co-treatment with GF109203X and H-89. PMA, a PKC activator, or forskolin, an activator of adenylate cyclase, on the other hand, reduced heat-activated outward currents and co-treatment with PMA and forskolin further attenuated the currents to an extent similar to that for noradrenaline.


CONCLUSIONS
The results of the present study show that heat-activated K+ channel currents in DRG neurons are inhibited by both PKC and PKA as mediated via alpha1 and beta adrenergic receptors, respectively. This may represent a new insight into regulation of thermosensation via a noradrenergic pathway.
Yamamoto
Satoshi
S
Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
Kanno
Takeshi
T
Yamada
Kosaku
K
Yasuda
Yoshiyuki
Y
Nishizaki
Tomoyuki
T
D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006358:Hot Temperature; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D024683:Potassium Channels, Tandem Pore Domain; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; C103742:potassium channel protein TREK-1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs; D009638:Norepinephrine