Role of protein phosphatases in the modulation of neuronal membrane currents

Although much is known regarding the modulation of ion channels through protein phosphorylation, little is known about their dephosphorylation by protein phosphatases (PrPs). To address this issue we examined the effects of a phosphatase inhibitor, okadaic acid (OA), and protein phosphatases obtained from rabbit skeletal muscle on steady-state membrane current in voltage-clamped sensory neurons of Aplysia. In addition, we examined the ability of OA and PrPs to modulate serotonin (5-HT)- and cAMP-induced inward currents and an opposite outward current induced by the peptide FMRFamide. The results suggest that: (1) some basal level of phosphorylation regulates membrane channels even in the absence of physiological stimulation; (2) the 5-HT-, cAMP-, and FMRFamide-induced responses are highly regulated by PrPs; and (3) the FMRFamide-induced outward current may be due at least in part to the activation of PrPs.