title: Differential responses of bladder lumbosacral and thoracolumbar dorsal root ganglion neurons to purinergic agonists, protons, and capsaicin.
abstract: The present study explored differences in sensitivity to purinergic agonists, protons, and capsaicin in lumbosacral (LS) and thoracolumbar (TL) sensory neurons that innervate the rat urinary bladder. The majority of LS neurons (93%) were sensitive to alpha,beta-methyleneATP (alpha,beta-metATP) compared with 50% of TL neurons. Based on inactivation kinetics, a slowly desensitizing current evoked by alpha,beta-metATP predominated in LS neurons (86%) compared with mixed components that characterized TL neuron responses (58%). The density of the slowly desensitizing current was greater in LS than in TL neurons (LS, 34.4 +/- 5.3 pA/pF; TL, 2.5 +/- 0.8 pA/pF). Almost all neurons in both ganglia responded to protons and to capsaicin (LS, 100%; TL, 98%). Proton-activated currents in bladder sensory neurons exhibited distinct inactivation kinetics as fast, intermediate, slowly desensitizing, and sustained components. More than one component was expressed in every cell. Although there was no difference in the percentage of neurons expressing more than one component, the density of the sustained current was significantly greater in LS than in TL neurons (LS, 86.1 +/- 16 pA/pF; TL, 30.3 +/- 7 pA/pF). Similarly, the capsaicin-evoked current was greater in LS than in TL neurons (LS, 129.6 +/- 17 pA/pF; TL, 86.9 +/- 11 pA/pF). Finally, a greater percentage of TL neurons bound isolectin B4 than LS neurons (LS, 61%; TL, 85%). The greater degree of alpha,beta-metATP, proton, and capsaicin responsiveness, in addition to differences in current type and current densities, in LS and TL neurons suggests that bladder pelvic and hypogastric/lumbar splanchnic afferents are functionally distinct and likely mediate different sensations arising from the urinary bladder.
authors.affiliation: Department of Pharmacology, The University of Iowa, Iowa City, Iowa 52242, USA. khoa-dang@uiowa.edu
authors.forename: Khoa
authors.initials: K
authors.lastname: Dang
authors.forename: Klaus
authors.initials: K
authors.lastname: Bielefeldt
authors.forename: G F
authors.initials: GF
authors.lastname: Gebhart
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry / Q000379:methods; D037102:Lectins / Q000378:metabolism; D008161:Lumbosacral Region; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009475:Neurons, Afferent / Q000145:classification / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D010636:Phenols / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology; D011522:Protons; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism; D013904:Thoracic Vertebrae; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology
chemical_list: C470346:A-317491; D000596:Amino Acids; D004791:Enzyme Inhibitors; D037102:Lectins; D010636:Phenols; D011083:Polycyclic Compounds; D011522:Protons; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D026941:Sodium Channel Blockers; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C098463:dolaisoleucine; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000584:Amiloride; D000255:Adenosine Triphosphate; C071423:capsazepine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002211:Capsaicin