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KATP Current (katp + current)
Selected AbstractsFew cultured rat primary sensory neurons express a tolbutamide-sensitive K+ currentJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2002Violeta Ristoiu Abstract The response of dorsal root ganglion (DRG) neurons to metabolic inhibition is known to involve calcium-activated K+ channels; in most neuronal types ATP-sensitive K+ channels (KATP) also contribute, but this is not yet established in the DRG. We have investigated the presence of a KATP current using whole-cell recordings from rat DRG neurons, classifying the neurons functionally by their "current signature" (Petruska et al, J Neurophysiol 84: 2365,2379, 2000). We clearly identified a KATP current in only 1 out of 62 neurons, probably a nociceptor. The current was activated by cyanide (2 mM NaCN) and was sensitive to 100 ,M tolbutamide; the relation between reversal potential and external K+ concentration indicated it was a K+ current. In a further two neurons, cyanide activated a K+ current that was only partially blocked by tolbutamide, which may also be an atypical KATP current. We conclude that KATP channels are expressed in normal DRG, but in very few neurons and only in nociceptors. [source] Dualistic actions of cromakalim and new potent 2H -1,4-benzoxazine derivatives on the native skeletal muscle KATP channelBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2003Domenico Tricarico New 2H -1,4-benzoxazine derivatives were synthesized and tested for their agonist properties on the ATP-sensitive K+ channels (KATP) of native rat skeletal muscle fibres by using the patch-clamp technique. The novel modifications involved the introduction at position 2 of the benzoxazine ring of alkyl substituents such as methyl (,CH3), ethyl (,C2H5) or propyl (,C3H7) groups, while maintaining pharmacophore groups critical for conferring agonist properties. The effects of these molecules were compared with those of cromakalim in the presence or absence of internal ATP (10,4M). In the presence of internal ATP, all the compounds increased the macropatch KATP currents. The order of potency of the molecules as agonists was ,C3H7 (DE50=1.63 × 10,8M) >,C2H5 (DE50=1.11 × 10,7M)>,CH3 (DE50=2.81 × 10,7M)>cromak-slim (DE50= 1.42 × 10,5M). Bell-shaped dose,response curves were observed for these compounds and cromakalim indicating a downturn in response when a certain dose was exceeded. In contrast, in the absence of internal ATP, all molecules including cromakalim inhibited the KATP currents. The order of increasing potency as antagonists was cromakalim (IC50=1.15 × 10,8M),CH3 (IC50=2.6 × 10,8M)>,C2H5 (IC50=4.4 × 10,8M)>,C3H7 (IC50=1.68 × 10,7M) derivatives. These results suggest that the newly synthesized molecules and cromakalim act on muscle KATP channel by binding on two receptor sites that have opposite actions. Alternatively, a more simple explanation is to consider the existence of a single site for potassium channel openers regulated by ATP which favours the transduction of the channel opening. The alkyl chains at position 2 of the 2H -1,4-benzoxazine nucleus is pivotal in determining the potency of benzoxazine derivatives as agonists or antagonists. British Journal of Pharmacology (2003) 139, 255,262. doi:10.1038/sj.bjp.0705233 [source] | ||||||||||