Abstract 817: ASIC2 Expression Is an Important Determinant of Mechanotransduction in Nodose Neurons
The ionic determinants of mechanotransduction in baroreceptor neurons have not been elucidated. We have shown that members of the DEG/ENaC family of ion channels (ASICs) are expressed in baroreceptor terminals and in nodose ganglia. In ASIC2 KO mice we also found suppressed activity of aortic depressor nerves in response to increases in arterial pressure during phenylephrine infusions. In these experiments we correlate the magnitude of expression of ASIC2 with the magnitude of mechanically induced depolarization in nodose neurons. Isolated nodose neurons from ASIC2−/− mice (n=23), wild type (WT, n=24) and transgenic mice overexpressing ASIC2 (Tg, n=14) were impaled with sharp microelectrodes and mechanically stimulated by puffing buffer solutions from a microinjection pipette at 10 psi. In a current clamp mode the depolarizations were significantly different between the three groups averaging 0.86 ± 0.53 mV, 2.72 ± 0.37 mV and 11.24 ± 2.2 mV in ASIC2−/−, WT and Tg, respectively. The figure portrays responses of a representative neuron from each group and indicates that in the Tg neuron the magnitude as well as the duration of depolarization were significantly greater (P<0.05) compared to the WT and KO. On the other hand, the excitability of these 3 groups of neurons in response to current injections was greatest in ASIC2− /− and was inversely related to their mechanosensitivity. We conclude that ASIC2 ion channels are important components of the mechanosensitive complex and may determine baroreceptor sensitivity.