Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder.

Mar 23, 2007Indian journal of experimental biology

How KATP channel openers affect muscle and nerve control in the goat bladder

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Abstract

The goat detrusor muscle exhibited a mean spontaneous contraction amplitude of 11.99 mm and a frequency of 1.37/min.

Cromakalim and pinacidil inhibited both the amplitude and rate of spontaneous contractions in a concentration-dependent manner.
The mean IC50 values for cromakalim were 3.3 x 10(-6) M for amplitude and 2.9 x 10(-6) M for frequency, while pinacidil had IC50 values of 2.0 x 10(-5) M for amplitude and 1.5 x 10(-5) M for frequency.
Glibenclamide, a KATP-channel blocker, significantly increased the mean IC50 for the relaxation of spontaneous contractions induced by cromakalim.
Cromakalim and pinacidil also inhibited the contractile response to acetylcholine (ACh), increasing the mean EC50 value for ACh in the presence of cromakalim from 1.2 x 10(-6) M to 2.5 x 10(-3) M.
Electrical field stimulation (EFS) induced frequency-related contractile responses, which were inhibited more by cromakalim than by pinacidil.
In the presence of glibenclamide, the inhibitory effect on the frequency-related contractile response was reduced, shifting the curve to the left.

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Isolated goat detrusor muscle exhibited spontaneous contractility with an irregular amplitude and frequency. The spontaneity of detrusor muscle exhibited a mean amplitude as 11.99 +/- 0.83 mm and frequency as 1.37 +/- 0.16/min. KATP-channel openers namely, cromakalim or pinacidil (10(-7) - 10(-4) M) added cumulatively, elicited a concentration-related inhibition of both amplitude and rate of spontaneous contractions. The mean IC50 values for both amplitude and frequency for cromakalim were 3.3 x 10(-6) M and 2.9 x 10(-6) M, respectively; and for pinacidil were 2.0 x 10(-5) M and 1.5 x 10(-5) M, respectively. Glibenclamide, a KATP-channel blocker inhibited the cromakalim-induced concentration-related relaxation of spontaneous contractions with a significant increase in its mean IC50. ACh-induced concentration-related contractile response was inhibited in the presence of either cromakalim (10(-4) M) or pinacidil (10(-4) M). The mean EC50 value of ACh, in the presence of cromakalim (2.5 x 10(-3) M) was significantly increased as compared to the control (1.2 x 10(-6) M). In the presence of glibenclamide (10(-5) M) the inhibitory effect of cromakalim was significantly reduced with consequent decrease in the EC50 value (1.9 x 10(-5) M). Application of EFS (30 V and 5 ms) on goat urinary bladder strips at 1, 2, 5, 10, 20 and 30 Hz elicited frequency-related contractile responses. Both cromakalim and pinacidil caused a rightward shift in the frequency-related contractile response curve with significant increase in the mean EF25 and EF50 values, respectively. In the presence of glibenclamide (10(-4) M), the frequency-related inhibitory response curve was shifted to left with significant (P < 0.001) increase in the mean EF25, EF50 and EF75. The present results suggest that in the goat detrusor muscle, agonist and EFS-induced contractile responses were more potently inhibited by cromakalim than pinacidil with activation of glibenclamide sensitive KATP channels.

Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder.

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