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Klaus Bielefeldt, Noriyuki Ozaki, Gerald F. Gebhart  Gastroenterology 

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Presentation on theme: "Klaus Bielefeldt, Noriyuki Ozaki, Gerald F. Gebhart  Gastroenterology "— Presentation transcript:

1 Mild gastritis alters voltage-sensitive sodium currents in gastric sensory neurons in rats 
Klaus Bielefeldt, Noriyuki Ozaki, Gerald F. Gebhart  Gastroenterology  Volume 122, Issue 3, Pages (March 2002) DOI: /gast Copyright © 2002 American Gastroenterological Association Terms and Conditions

2 Fig. 1 Effect of iodoacetamide on gastric mucosa. Photomicrographs were obtained at 100× magnification, showing representative sections of the glandular stomach obtained from (A) a control animal and (B) a rat treated with 0.1% iodoacetamide in the drinking water for 7 days. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Identification of cultured gastric sensory neurons. (A) Three dorsal neurons were photographed under Hoffman optics (400×) 4 hours after dissociation. (B) Only one of these cells was DiI-labeled (arrow), as identified by the fluorescence under UV light with a rhodamine filter with excitation wavelength ~546 nm and barrier filter at 580 nm. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Voltage-sensitive currents in primary gastric sensory neurons. Inward and outward currents were evoked by depolarizing (A) DRG or (B) nodose neurons from −50 mV to 10 mV. Representative current traces show cells (a) with and (b) without a transient component of the outward current. Current-voltage relationships for the inward current (▾), the peak (●), and sustained outward current (○) were constructed for (C) DRG and (D) nodose neurons by stepping the cells from −50 mV to various test potentials between −60 and 50 mV. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Effect of iodoacetamide on inward currents in primary gastric sensory neurons. Voltage-sensitive inward currents were triggered in (A) nodose and (B) DRG neurons by stepping cells from a −50 mV to various test potentials between −60 and 50 mV. The current voltage-relationship was constructed for cells obtained from control (●) and iodoacetamide-treated animals (○). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Effect of iodoacetamide on outward currents in primary gastric sensory neurons. Current voltage relationships for the peak and sustained outward current were constructed for cells obtained from control (●) and iodoacetamide-treated animals (○). The currents were triggered in (A and B) nodose and (C and D) DRG neurons by stepping cells from a −50 mV to various test potentials between −60 and 50 mV. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

7 Fig. 6 Effects of iodoacetamide on voltage-dependent sodium currents. Sodium currents were triggered by depolarizing cells from −70 mV to 0 mV. Currents were recorded in the (top) absence and (middle) presence of 1 μmol/L TTX. To obtain the TTX-sensitive current (bottom), the TTX-resistant current was digitally subtracted from the whole sodium current. Representative traces from control neurons are shown on the left, whereas the traces on the right were obtained from a neuron harvested from an iodoacetamide-treated animal. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

8 Fig. 7 Effect of iodoacetamide on peak sodium currents. Sodium currents were triggered by depolarization from −70 mV to 0 mV. The (A) upper panel shows the peak current measured for DRG neurons from control (■; n = 16) or iodoacetamide-treated (□; n = 16) animals and nodose neurons from control (■; n = 29) or iodoacetamide-treated (□; n = 21) animals. Panels B and C show peak amplitudes of the pharmacologically distinct sodium currents under control conditions (■) and after iodoacetamide treatment (□). In (B) DRG neurons, iodoacetamide exposure increased the TTX-resistant current (n = 16) compared with controls (n = 14). The TTX-sensitive current did not differ between controls (n = 7) and cells from iodoacetamide-treated animals (n = 10). In (C) nodose neurons, iodoacetamide did not affect TTX-resistant (control: n = 13; iodoacetamide: n = 13) or TTX-sensitive current (control: n = 18; iodoacetamide: n = 12). *P < 0.05. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

9 Fig. 8 Effect of iodoacetamide on voltage-dependence of sodium currents in DRG neurons. To determine the voltage-dependence of activation, cells were depolarized from −70 mV to various test potentials between −60 and 50 mV. The normalized conductance was calculated and plotted as a function of the test potential. The voltage-dependence of inactivation was determined by holding cells for 750 ms at various potentials between −110 and 10 mV before stepping to the same test potential of 20 mV. The peak current triggered by the step to 20 mV was normalized and plotted as a function of the prepotential. The results were fitted with the Boltzmann equation (see text for details). Data for (A and B) TTX-sensitive and (C and D) the TTX-resistant are given for control cells (■) and cells obtained from iodoacetamide-treated animals (□). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

10 Fig. 9 Effect of iodoacetamide on voltage-dependence of sodium currents in nodose neurons. To determine the voltage-dependence of activation, cells were depolarized from −70 mV to various test potentials between −60 and 50 mV. The normalized conductance was calculated and plotted as a function of the test potential. The voltage-dependence of inactivation was determined by holding cells for 750 ms at various potentials between −110 and 10 mV before stepping to the same test potential of 20 mV. The peak current triggered by the step to 20 mV was normalized and plotted as a function of the prepotential. The results were fitted with the Boltzmann equation (see text for details). Data for (A and B) TTX-sensitive and (C and D) the TTX-resistant are given for control cells (■) and cells obtained from iodoacetamide-treated animals (□). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions


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