The cAMP transduction cascade mediates the PGE2-induced inhibition of potassium currents in rat sensory neurones

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Abstract

1. The role of the cyclic AMP (cAMP) transduction cascade in mediating the prostaglandin E2 (PGE2)-induced decrease in potassium current (I(K)) was investigated in isolated embryonic rat sensory neurones using the whole-cell patch-clamp recording technique. 2. Exposure to 100 μM chlorophenylthio-adenosine cyclic 3',5'-monophosphate (cpt-cAMP) or 1 μM PGE2 caused a slow suppression of the a hole-cell I(K) by 34 and 36%, respectively (measured after 20 min), without a shift in the voltage dependence of activation for this current. Neither of these agents altered the shape of the voltage-dependent inactivation curve indicating that the suppression of I(K) did not result from alterations in the inactivation properties. 3. To determine whether the PGE2-mediated suppression of I(K) depended on activation of the cAMP pathway, cells were exposed to this prostanoid in the presence of the protein kinase A (PKA) inhibitor, PKI. The PGE2-induced suppression of I(K) was prevented by PKI. In the absence of PGE2, PKI had no significant effect on the magnitude of I(K). 4. Results obtained from protocols using different conditioning prepulse voltages indicated that the extent of cpt-cAMP- and PGE2-mediated suppression of I(K) was independent of the prepulse voltage. The subtraction of control and treated currents revealed that the cpt-cAMP- and PGE2-sensitive currents exhibited little time-dependent inactivation. Taken together, these results suggest that the modulated currents may be delayed rectifier-like I(K). 5. Exposure to the inhibitors of I(K), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), reduced the control current elicited by a voltage step to +60 mV by 40-50%. In the presence of 10 mM TEA, treatment with cpt-cAMP did not result in any further inhibition of I(K). In contrast, cpt-cAMP reduced I(K) by an additional 25-30% in the presence of 1 mM 4-AP. This effect was independent of the conditioning prepulse voltage. 6. These results establish that PGE2 inhibits an outward I(K) in sensory neurones via activation of PKA and are consistent with the idea that the PGE2-mediated sensitization of sensory neurones results, in part, from an inhibition of delayed rectifier-like I(K).

Original languageEnglish
Pages (from-to)163-178
Number of pages16
JournalJournal of Physiology
Volume516
Issue number1
StatePublished - Apr 1 1999

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Sensory Receptor Cells
Dinoprostone
Cyclic AMP
Potassium
4-Aminopyridine
Tetraethylammonium
Cyclic AMP-Dependent Protein Kinases
Patch-Clamp Techniques
Protein Kinase Inhibitors
Prostaglandins

ASJC Scopus subject areas

  • Physiology

Cite this

The cAMP transduction cascade mediates the PGE2-induced inhibition of potassium currents in rat sensory neurones. / Evans, A. R.; Vasko, Michael; Nicol, Grant.

In: Journal of Physiology, Vol. 516, No. 1, 01.04.1999, p. 163-178.

Research output: Contribution to journalArticle

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abstract = "1. The role of the cyclic AMP (cAMP) transduction cascade in mediating the prostaglandin E2 (PGE2)-induced decrease in potassium current (I(K)) was investigated in isolated embryonic rat sensory neurones using the whole-cell patch-clamp recording technique. 2. Exposure to 100 μM chlorophenylthio-adenosine cyclic 3',5'-monophosphate (cpt-cAMP) or 1 μM PGE2 caused a slow suppression of the a hole-cell I(K) by 34 and 36{\%}, respectively (measured after 20 min), without a shift in the voltage dependence of activation for this current. Neither of these agents altered the shape of the voltage-dependent inactivation curve indicating that the suppression of I(K) did not result from alterations in the inactivation properties. 3. To determine whether the PGE2-mediated suppression of I(K) depended on activation of the cAMP pathway, cells were exposed to this prostanoid in the presence of the protein kinase A (PKA) inhibitor, PKI. The PGE2-induced suppression of I(K) was prevented by PKI. In the absence of PGE2, PKI had no significant effect on the magnitude of I(K). 4. Results obtained from protocols using different conditioning prepulse voltages indicated that the extent of cpt-cAMP- and PGE2-mediated suppression of I(K) was independent of the prepulse voltage. The subtraction of control and treated currents revealed that the cpt-cAMP- and PGE2-sensitive currents exhibited little time-dependent inactivation. Taken together, these results suggest that the modulated currents may be delayed rectifier-like I(K). 5. Exposure to the inhibitors of I(K), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), reduced the control current elicited by a voltage step to +60 mV by 40-50{\%}. In the presence of 10 mM TEA, treatment with cpt-cAMP did not result in any further inhibition of I(K). In contrast, cpt-cAMP reduced I(K) by an additional 25-30{\%} in the presence of 1 mM 4-AP. This effect was independent of the conditioning prepulse voltage. 6. These results establish that PGE2 inhibits an outward I(K) in sensory neurones via activation of PKA and are consistent with the idea that the PGE2-mediated sensitization of sensory neurones results, in part, from an inhibition of delayed rectifier-like I(K).",
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N2 - 1. The role of the cyclic AMP (cAMP) transduction cascade in mediating the prostaglandin E2 (PGE2)-induced decrease in potassium current (I(K)) was investigated in isolated embryonic rat sensory neurones using the whole-cell patch-clamp recording technique. 2. Exposure to 100 μM chlorophenylthio-adenosine cyclic 3',5'-monophosphate (cpt-cAMP) or 1 μM PGE2 caused a slow suppression of the a hole-cell I(K) by 34 and 36%, respectively (measured after 20 min), without a shift in the voltage dependence of activation for this current. Neither of these agents altered the shape of the voltage-dependent inactivation curve indicating that the suppression of I(K) did not result from alterations in the inactivation properties. 3. To determine whether the PGE2-mediated suppression of I(K) depended on activation of the cAMP pathway, cells were exposed to this prostanoid in the presence of the protein kinase A (PKA) inhibitor, PKI. The PGE2-induced suppression of I(K) was prevented by PKI. In the absence of PGE2, PKI had no significant effect on the magnitude of I(K). 4. Results obtained from protocols using different conditioning prepulse voltages indicated that the extent of cpt-cAMP- and PGE2-mediated suppression of I(K) was independent of the prepulse voltage. The subtraction of control and treated currents revealed that the cpt-cAMP- and PGE2-sensitive currents exhibited little time-dependent inactivation. Taken together, these results suggest that the modulated currents may be delayed rectifier-like I(K). 5. Exposure to the inhibitors of I(K), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), reduced the control current elicited by a voltage step to +60 mV by 40-50%. In the presence of 10 mM TEA, treatment with cpt-cAMP did not result in any further inhibition of I(K). In contrast, cpt-cAMP reduced I(K) by an additional 25-30% in the presence of 1 mM 4-AP. This effect was independent of the conditioning prepulse voltage. 6. These results establish that PGE2 inhibits an outward I(K) in sensory neurones via activation of PKA and are consistent with the idea that the PGE2-mediated sensitization of sensory neurones results, in part, from an inhibition of delayed rectifier-like I(K).

AB - 1. The role of the cyclic AMP (cAMP) transduction cascade in mediating the prostaglandin E2 (PGE2)-induced decrease in potassium current (I(K)) was investigated in isolated embryonic rat sensory neurones using the whole-cell patch-clamp recording technique. 2. Exposure to 100 μM chlorophenylthio-adenosine cyclic 3',5'-monophosphate (cpt-cAMP) or 1 μM PGE2 caused a slow suppression of the a hole-cell I(K) by 34 and 36%, respectively (measured after 20 min), without a shift in the voltage dependence of activation for this current. Neither of these agents altered the shape of the voltage-dependent inactivation curve indicating that the suppression of I(K) did not result from alterations in the inactivation properties. 3. To determine whether the PGE2-mediated suppression of I(K) depended on activation of the cAMP pathway, cells were exposed to this prostanoid in the presence of the protein kinase A (PKA) inhibitor, PKI. The PGE2-induced suppression of I(K) was prevented by PKI. In the absence of PGE2, PKI had no significant effect on the magnitude of I(K). 4. Results obtained from protocols using different conditioning prepulse voltages indicated that the extent of cpt-cAMP- and PGE2-mediated suppression of I(K) was independent of the prepulse voltage. The subtraction of control and treated currents revealed that the cpt-cAMP- and PGE2-sensitive currents exhibited little time-dependent inactivation. Taken together, these results suggest that the modulated currents may be delayed rectifier-like I(K). 5. Exposure to the inhibitors of I(K), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), reduced the control current elicited by a voltage step to +60 mV by 40-50%. In the presence of 10 mM TEA, treatment with cpt-cAMP did not result in any further inhibition of I(K). In contrast, cpt-cAMP reduced I(K) by an additional 25-30% in the presence of 1 mM 4-AP. This effect was independent of the conditioning prepulse voltage. 6. These results establish that PGE2 inhibits an outward I(K) in sensory neurones via activation of PKA and are consistent with the idea that the PGE2-mediated sensitization of sensory neurones results, in part, from an inhibition of delayed rectifier-like I(K).

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