Regulation of cAMP-stimulated ion current by intracellular pH, Ca2+, and calmodulin blockers

D. J. Green, R. Gillette

Research output: Contribution to journalArticlepeer-review


1. Iontophoretic injection of adenosine 3',5'-cyclic monophosphate (cAMP) into identified neurons elicited a slow transient Na+ current whose amplitude and duration were sensitive to altered intracellular pH (pH(i)), calmodulin blocking drugs, depolarization, and manipulations of internal and external Ca2+. 2. Intracellular acidification between resting pH(i) to several tenths of a pH unit increased the amplitude of the cAMP-stimulated current and prolonged its duration. 3. Intracellular alkalinization of similar magnitude also increased the amplitude and duration of the current response. The effects of alkalinization were somewhat labile. In cells alkalinized by NH4+-containing salines, washout of NH4+ with normal saline caused acidification and further enhanced the cAMP current response. The immediacy of the increase and the dual acid/basic sensitivity of the response suggest an accommodative process whereby the responsiveness of the cell to cAMP adapts to a maintained pH(i). 4. The calmodulin blockers trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide increased the amplitude and duration of the current response. Phorbol ester activators of Ca2+/phospholipid-dependent kinase had no effect on the current. 5. Periods of depolarization preceding tests significantly reduced current response amplitude. This effect was dependent on saline Ca2+ and was blocked by Co2+. 6. Intracellular injection of the Ca2+ chelator ethylene glycol-bis(β-aminoethyl ether)N,N,N',N',-tetraacetic acid also augmented the amplitude and duration of the current response. 7. The above effects are consistent with a possible common site of action on cAMP degradation. This interpretation is consistent with previous evidence for pH-sensitive and Ca2+/calmodulin-dependent cAMP phosphodiesterase activity in Pleurobranchaea nervous tissue.

Original languageEnglish (US)
Pages (from-to)248-258
Number of pages11
JournalJournal of neurophysiology
Issue number1
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


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