Dual regulation by protein kinase C of the muscarinic response in Xenopus oocytes

Monica Lupu-Meiri, Hagit Shapira, Yoram Oron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Muscarinic stimulation of follicle-enclosed oocytes of Xenopus laevis results in a complex response that involves both depolarizing and hyperpolarizing currents (Dascal and Landau 1980). We studied the involvement of protein kinase C (PK-C1) in the regulation of the acetylcholine-evoked rapid (D1) and of the slow (D2) depolarizing chloride (Cl-) currents. In oocytes maintained at -100 mV [the reversal potential of potassium (K+) ions] under two electrode voltage clamp, the PK-C activator 4-β-phorbol 12-myristate 13-acetate (β-PMA, 0.1 μM) stimulated D1 by 99±17% and inhibited D2 by 67±6%, vs. untreated controls. The inactive isomer (α-PMA) or phorbol alone had no significant effect on the components of the muscarinic response. In order to identify the site of the regulation, we have microinjected the intracellular second messenger of calcium mobilization, inositol 1,4,5-trisphosphate (IP3). β-PMA or the diacylglycerol analog, oleoylacetylglycerol (OAG) stimulated the rapid depolarizing current evoked by IP3 by 220±26% and 394±102%, respectively. α-PMA had little if any effect. The calcium-evoked Cl- current in oocytes pre-treated with the divalent cation ionophore A23187 was, on the other hand, inhibited by β-PMA and OAG (by 82±6% and 54±6%, respectively). α-PMA and phorbol had a limited inhibitory effect. β-PMA, but not α-PMA, also mildly inhibited the IP3-evoked increase in45Ca efflux. The intracellular metabolism of IP3 was not affected by exposure to either β-PMA or OAG. In conclusion, PK-C appears to regulate the acetylcholine-evoked Cl- response in a complex pattern: inhibition of the slow (D2) Cl- current (possibly directly on the Cl- channel) and stimulation of the rapid (D1) Cl- current. Both sites of regulation seem to be distal to IP3 metabolism and to IP3-evoked calcium mobilization. Our results are consistent with the possibility that the complex muscarinic response in Xenopus oocyte is mediated by two populations of Cl- channels.

Original languageEnglish
Pages (from-to)498-504
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Issue number5
StatePublished - Mar 1989


  • Calcium
  • Chloride current
  • Inositol trisphosphate
  • Muscarinic response
  • Protein kinase C
  • Xenopus oocytes


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