Protein kinase A cascade regulates quantal release dispersion at frog muscle endplate.
Uniquantal endplate currents (EPCs) were recorded simultaneously at the proximal, central and distal parts of the frog neuromuscular synapse, and their minimal synaptic latencies, latency dispersions and sensitivity to noradrenaline, cAMP and protein kinase A inhibition were measured. The latency dispersion was highest in the proximal part (P90 = 1.25 ms); it decreased to P90 = 0.95 ms in the central part and to P90 = 0.75 ms (60 % of the proximal part) in the distal part. In the proximal parts of the long neuromuscular synapse, stimulation-evoked EPCs with long release latencies were eliminated when the intracellular cAMP was increased by beta1 activation by noradrenaline, by the permeable analogue db-cAMP, by activation of adenylyl cyclase or by inhibition of cAMP hydrolysis. This makes the evoked release more compact, and the amplitude of the reconstructed multiquantal currents increases. Protein kinase A is a target of this regulation, since a specific inhibitor, Rp-cAMP, prevents the action of cAMP in the proximal parts and increases the occurrence of long-latency events in the distal parts of the synapse. Our results show that protein kinase A is involved in the timing of quantal release and can be regulated by presynaptic adrenergic receptors.
Bukharaeva
Ella A
EA
State Medical University, Butlerov st. 49, Kazan, Russian Federation and Institute of Biochemistry and Biophysics, Russian Academy of Sciences, PO Box 30, Kazan, Russian Federation.
Samigullin
Dmitry
D
Nikolsky
Eugeny
E
Vyskocil
Frantisek
F
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009045:Motor Endplate / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011312:Pressure; D011895:Rana ridibunda; D011930:Reaction Time / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D000244:Adenosine Diphosphate; D003994:Bucladesine; C010840:adenosine 3'-phosphate-5'-phosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine