Direct assessment of tubuloglomerular feedback responsiveness in connexin 40-deficient mice

作者：Oppermann Mona; Carota Isabel; Schiessl Ina; Eisner Christoph; Castrop Hayo; Schnermann Jurgen^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2013, 304(9): F1181-F1186.

DOI：10.1152/ajprenal.00721.2012

• micropuncture
• stop-flow pressure
• genetic background
• vascular resistance

Participation of connexin 40 (Cx40) in the regulation of renin secretion and in the tubuloglomerular feedback (TGF) component of renal autoregulation suggests that gap junctional coupling through Cx40 contributes to the function of the juxtaglomerular apparatus. In the present experiments, we determined the effect of targeted Cx40 deletion in C57BL/6 and FVB mice on TGF responsiveness. In C57BL/6 mice, stop-flow pressure (P-SF) fell from 40.3 +/- 2 to 34.5 +/- 2 mmHg in wild-type (WT) and from 31 +/- 1.06 to 26.6 +/- 0.98 mmHg in Cx40-/- mice. PSF changes of 5.85 +/- 0.67 mmHg in WT and of 4.3 +/- 0.55 mmHg in Cx40-/- mice were not significantly different (P = 0.08). In FVB mice, P-SF fell from 37.4 +/- 1.5 to 31.6 +/- 1.5 mmHg in WT and from 28.1 +/- 1.6 to 25.4 +/- 1.7 mmHg in Cx40-/-, with mean TGF responses being significantly greater in WT than Cx40-/- (5.5 +/- 0.55 vs. 2.7 +/- 0.84 mmHg; P = 0.002). In both genetic backgrounds, PSF values were significantly lower in Cx40-/- than WT mice at all flow rates. Arterial blood pressure in the animals prepared for micropuncture was not different between WT and Cx40-/- mice. We conclude that the TGF response magnitude in superficial cortical nephrons is reduced by 30-50% in mice without Cx40, but that with the exception of a small number of nephrons, residual TGF activity is maintained. Thus gap junctional coupling appears to modulate TGF, perhaps by determining the kinetics of signal transmission.

• 出版日期2013-5
• 单位NIH