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The Journal of Neuroscience, April 13, 2005, 25(15):3973-3984; doi:10.1523/JNEUROSCI.5239-04.2005

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Cellular/Molecular
Differential Responses of Bladder Lumbosacral and Thoracolumbar Dorsal Root Ganglion Neurons to Purinergic Agonists, Protons, and Capsaicin

Khoa Dang,¹ Klaus Bielefeldt,² and G. F. Gebhart¹

¹Department of Pharmacology, The University of Iowa, Iowa City, Iowa 52242, and ²Department of Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 16213

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 ,-methyleneATP (,-metATP) compared with 50% of TL neurons. Based on inactivation kinetics, a slowly desensitizing current evoked by ,-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 ,-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.

Key words: bladder; dorsal root ganglia; ,-metATP; ATP; P2X receptors; protons; capsaicin; IB4; A317491

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Received Dec 22, 2004; revised March 9, 2005; accepted March 9, 2005.

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