Influences of pressure-injected cyclic AMP on the membrane current and characteristics of an identified neuron of Aplysia kurodai.

Abstract

The ionic mechanism of the effect of intracellularly injected adenosine 3',5'-cyclic monophosphate (CAMP) on the membrane of identified neuron L5 of Apl ysia kurodai was investigated with conventional voltage-clamp and ion-substitution techniques. The intracellular elevation of CAMP caused an inward current ('CAMP), which was not accompanied by a significant change in membrane conductance at potentials more hyperpolarized than -60 mV. The current increased over the voltage range (-50 to -30 mV) associated with a conductance decrease and decreased at potentials more hyperpolarized than -60 mV. Elevated intracellular CAMP was found to enhance a region of negative slope resistance in steady-state I -V relations. Duration of the 'CAMP was greatly prolonged by bath-applied isobutylmethylxanthine (50 ,uM), but imidazole (10 mM) had an opposite effect on the 'CAMP. Tolbutamide (5 mM), a protein kinase inhibitor, reduced the DAMP. The current was not affected by the presence of bath-applied TTX (50 µM), ouabain (50 /LM), or triaminopyrimidine (5 mM). Reduction of [Na+]o reversibly decreased the DAMP. Li+ could largely substitute for Nat Alterations of [K+]o, and bath application of 4-AP (5 mM) and TEA (30 mM) did not affect the DAMP, In the presence of Nat, Cl-, and divalent cations such as Ca2+ and Ba2+ inhibited the DAMP. These results suggest that fast elevation of intracellular cAMP induces a TTX-resistant slow Na+ inward current, and the current might be due to activation of CAMP-dependent protein kinase.

Co‐regulation of cAMP‐activated Na+ current by Ca2+ in neurones of the mollusc Pleurobranchaea.

“…A slow Na+ current activated by cAMP (INa, cAMP) is a prominent neuromodulatory feature in many molluscan neurons (Liberman, Minina & Golubtsov, 1975; Aldenhoff, Hofmeier, Lux & Swandulla, 1983;Green & Gillette, 1983; Kononenko, Kostyuk & R. -C. HUANG AND R. GILLETTE Shcherbatko, 1983;Connor & Hockberger, 1984;Hara, Sawada & Maeno, 1985; Huang & Gillette, 1986; Swandulla, 1987; McCrohan & Gillette, 1988;Ichinose & McAdoo, 1989; Kehoe, 1990a). It contributes to endogenously rhythmic bursting mechanisms in single neurons (Green & Gillette, 1983), to aspects of behavioural arousal in neuronal networks (Gillette, 1988), and to synaptic mechanisms of neuromodulation (Huang & Gillette, 1986;Kehoe, 1990b).…”

“…Hill plots suggest that the stoichiometry of activation of INa, CAMP is one molecule of cAMP to one INa, CAMP channel (Huang & Gillette, 1991 (Green & Gillette, 1983;Connor & Hockerberg, 1984;Hara et al 1985;Ichinose & McAdoo, 1989). In other neurons the size of the current does not change between -100 and -20 mV (Aldenhoff et al 1983;Connor & Hockberger, 1984;McCrohan & Gillette, 1988).…”

Cyclic AMP-induced slow inward current in depolarized neurons of Aplysia californica

“…In molluscan neurons, many of these slow transmitter-induced changes in membrane conductance have been shown to be controlled by cyclic nucleotides (for reviews, see Connor and Hockberger, 1985;Lcvitan, 1985Lcvitan, , 1988Hockberger and Swandulla, 1987). One of these nucleotide-induced responses, seen as early as 1975 by Liberman et al, is a TTX-, ouabain-, and amiloride-insensitive slow inward current that is correlated with an increase in intracellular Na (Aldenhoff et al, 1983;Connor and Hockberger, 1984a) and disappears when extracellular Na is replaced by Tris (Kononenko et al, 1983;Connor and Hockberger, 1984a;Swandulla and Lux, 1984), TMA (Aldenhoff et al, 1983;Connor and Hockberger, 1984a), saccharose (Aldenhoff et al, 1983), bis-tris propane (Connor and Hockberger, 1984a), mannitol (Kehoe, 1985a), or glucosamine (Hara et al, 1985), but persists when Na is replaced by lithium (Aldenhoff et al, 1983;Connor and Hockberger, 1984a;Hara et al, 1985). A similar nucleotideinduced current has recently been described in photoreceptors (Fesenko et al, 1985;Haynes et al, 1986;Matthews and Watanabe, 1987) olfactory receptor cilia (Nakamura and Gold, 1987), and myocytes (Egan et al, 1988).…”

Forskolin mimics the dopamine-induced K+ conductance increase in identified neurons of Aplysia kurodai.

“…Recently it has been shown that extracellular application of PDE inhibitor (theophylline or IBMX) increased the amplitude of the cAMP-induced inward current. Imidazole, tolbutamide, and lowering the temperature reduced the amplitude of this current (KoNoNENxo et al, 1983;HARA et al, 1985). From such evidence it has been concluded that the cAMPinduced inward current is due to activation of a cAMP-dependent protein kinase in an identified Helix neuron (KoNoNENxo et al, 1983) and in an unidentified neuron L5 of Aplysia (HARA et al, 1985).…”

“…Imidazole, tolbutamide, and lowering the temperature reduced the amplitude of this current (KoNoNENxo et al, 1983;HARA et al, 1985). From such evidence it has been concluded that the cAMPinduced inward current is due to activation of a cAMP-dependent protein kinase in an identified Helix neuron (KoNoNENxo et al, 1983) and in an unidentified neuron L5 of Aplysia (HARA et al, 1985). Forskolin mimics the effects of DA by increasing the activity of adenylate cyclase through a direct activation of its catalytic subunit (SEAMON and WETZEL, 1984).…”