Abnormal excitability in capsaicin-responsive DRG neurons from cats with feline interstitial cystitis.
Interstitial cystitis (IC) is a painful disorder which affects urinary bladder function in cats and humans. We used patch clamp techniques to measure firing properties and K+ currents of dorsal root ganglion (DRG) neurons (L4-S3) from normal cats and cats with feline interstitial cystitis (FIC) to examine the possibility that the properties of primary afferent neurons are changed in cats with FIC. We found that capsaicin (CAPS)-responsive neurons from FIC cats were increased in size, had increased firing in response to depolarizing current pulses and expressed more rapidly inactivating K+ currents. CAPS-sensitive neurons from FIC cats were 28% larger than those from normal cats but were otherwise similar with respect to membrane potential and action potential (AP) threshold. CAPS-responsive neurons from normal cats fired 1.5 APs in response to a 600 ms depolarizing current pulse, 60-200 pA in intensity. The number of APs was increased 4.5 fold in FIC neurons. Neurons from FIC cats also exhibited after hyperpolarization potentials which were on the average 2x slower than those in normal cat neurons. In addition, there was a lack of K+ currents in the critical voltage range of action potential generation (between -50 to -30 mV). These changes were not detected in CAPS-unresponsive neurons from normal and FIC cats. Our data suggest that FIC afferent neurons exhibit abnormal firing which may be due to changes in the behavior of K+ currents and show that these changes are restricted to a subpopulation of CAPS-responsive neurons.
Sculptoreanu
Adrian
A
Department of Pharmacology, University of Pittsburgh, School of Medicine, W1354 Biomedical Science Tower, Pittsburgh, PA 15261, USA. ads5@pitt.edu
de Groat
William C
WC
Buffington
C A Tony
CA
Birder
Lori A
LA
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002415:Cats; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000503:physiopathology*; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000494:pharmacology; D013997:Time Factors
D011188:Potassium; D002211:Capsaicin