Our lab has recently reported that renal sensory nerve activity is increased in preclinical models of polycystic kidney disease (PKD), and contributes to renal cystic progression. Yet the underlying driver of this pathological sensory signaling remains unclear. Increased circulating vasopressin (AVP) is a known driver of renal cyst progression in PKD, but the effects of AVP on renal sensory nerve activity remains unclear – in health and disease conditions. We aimed to address this critical gap by measuring the electrophysiological response to AVP in primary isolated, renal-specific dorsal root ganglia neurons (rDRGNs) from healthy controls and from the PCK rat model of PKD. We hypothesized that AVP directly modulates the responsiveness of rDRGNs in non-cystic controls, and this effect is exacerbated in PKD. To test our hypothesis, we isolated primary rDRGNs from male Sprague-Dawley (SD) rats (n=8 cells from 4 rats; 12-13 weeks old), serving as non-cystic controls, and male PCK rats (n=8 cells from 4 rats; 9-11 weeks old), an established model of autosomal recessive PKD. DRGs were excised at necropsy and enzymatically digested and cultured overnight for whole-cell patch clamp recordings the next day. Renal-specific DRGNs were identified by fluorescent retrograde tracer (DiI), which was administered intrarenally 6 days prior to tissue collection. Cell excitability was measured in current-clamp mode via injections of 1 second long current steps, from -100 to +300 pA (20 pA increment). Excitability was measured by mean action potential (AP) frequency calculated across all cells at each current step value, at baseline and after application of 1 µM AVP. Mean resting membrane potential (mV) was also measured at baseline and following vasopressin application. Data were analyzed by two-way repeat-measures ANOVA, and main effects of treatment/strain were considered significant if p< .05. Data presented as mean±SEM. Within the SD cohort, rDRGN mean AP frequency was increased with AVP application compared to baseline (p< .05). No effect of AVP was detected on mean resting membrane potential compared to baseline (-50.44 ± 5.05 vs. -46.59. ± 1.99 mV; p=0.14). In the PCK group, similar to what was observed in the SD group, a main effect of AVP treatment was detected, where AP frequency across all current steps compared to baseline (p< .05). Moreover, mean resting membrane potential trended (p=.07) to lower in response to AVP compared to baseline (-54.86. ± 1.83 vs. -49.68 ± 1.82mV); however, this was not significant. Comparison between the SD and PCK groups showed that the mean AP frequency across all current steps was significantly higher in the PCK group (p< .05) for both baseline conditions and following application of AVP. Together, these data support our hypothesis that renal sensory nerve excitability is increased by AVP in healthy, non-cystic controls, and this effect is exaggerated in the PCK rat model of PKD. Moreover, we also show for the first time that the baseline rDRGN excitability is increased in the PCK rat compared to the non-cystic SD. These data complement our previous reports of progressive increases in renal sensory nerve activity in the PCK rat model, and we posit that AVP may be contributing to this effect. Studies are underway using voltage-clamp patch interrogation of the effects on ion channel activity as well as the vasopressin receptor type mediating these effects. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Hayoz et al. (Fri,) studied this question.