3-Isobutyl-1-methylxanthine (IBMX) affects potassium permeability in rat sensory neurones via pathways that are sensitive and insensitive to [Ca2+]in.
The effects of externally applied 3-isobutyl-1-methylxanthine (IBMX), in millimolar concentrations, on the membrane currents in dorsal root ganglia (DRG) neurones isolated from newborn rats were investigated using the amphotericin-based "perforated" patch-clamp technique. In some experiments, simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]in) were performed using fura-2 microfluorimetry. Applications of IBMX induced elevation of [Ca2+]in resulting from Ca2+ release from caffeine-ryanodine-sensitive internal stores. In addition to Ca2+ release, IBMX produced a biphasic membrane current response comprised of an inward current transiently interrupted by outward current. The onset of the inward current slightly preceded the onset of the [Ca2+]in transient, while the interrupting outward current developed synchronously with the [Ca2+]in rise. The development of IBMX-induced outward current ultimately needed the [Ca2+]in elevation. After the depletion of Ca2+ stores by IBMX or caffeine exposure, the subsequent IBMX challenge failed to produce both the [Ca2+]in transient and outward membrane current, although the inward current remained unchanged. Both components of the IBMX-induced membrane current response had a reversal potential close to the K+ equilibrium potential and the IBMX-induced membrane current response disappeared while dialysing the cell interior with K(+)-free, Cs(+)-containing solutions suggesting their association with K+ channel activity. External administration of 10 mM tetraethylammonium chloride (TEA-Cl) evoked an inward current similar to that observed in response to IBMX; in the presence of TEA-Cl, IBMX application was almost unable to induce additional inward current. IBMX (5 mM) effectively (approximately 50%) inhibited K+ currents evoked by step depolarizations of membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D016257:Fura-2; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology
D015220:Calcium Channels; D010726:Phosphodiesterase Inhibitors; D012433:Ryanodine; D002110:Caffeine; D011188:Potassium; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D016257:Fura-2