title: The biophysical and pharmacological characteristics of skeletal muscle ATP-sensitive K+ channels are modified in K+-depleted rat, an animal model of hypokalemic periodic paralysis.
abstract: We evaluated the involvement of the sarcolemmal ATP-sensitive K+ channel in the depolarization of skeletal muscle fibers occurring in an animal model of human hypokalemic periodic paralysis, the K+-depleted rat. After 23-36 days of treatment with a K+-free diet, an hypokalemia was observed in the rats. No difference in the fasting insulinemia and glycemia was found between normokalemic and hypokalemic rats. The fibers of the hypokalemic rats were depolarized. In these fibers, the current of sarcolemmal ATP-sensitive K+ channels measured by the patch-clamp technique was abnormally reduced. Cromakalim, a K+ channel opener, enhanced the current and repolarized the fibers. At channel level, two open conductance states blocked by ATP and stimulated by cromakalim were found in the hypokalemic rats. The two states could be distinguished on the basis of their slope conductance and open probability and were never detected on muscle fibers of normokalemic rats. It is known that insulin in humans affected by hypokalemic periodic paralysis leads to fiber depolarization and provokes paralysis. We therefore examined the effects of insulin at macroscopic and single-channel level on hypokalemic rats. In normokalemic animals, insulin applied in vitro to the muscles induced a glybenclamide-sensitive hyperpolarization of the fibers and also stimulated the sarcolemmal ATP-sensitive K+ channels. In contrast, in hypokalemic rats, insulin caused a pronounced fiber depolarization and reduced the residual currents. Our data indicated that in hypokalemic rats, an abnormally low activity of ATP-sensitive K+ channel is responsible for the fiber depolarization that is aggravated by insulin.
authors.affiliation: Unit of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, 70126 Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Tricarico
authors.forename: S
authors.initials: S
authors.lastname: Pierno
authors.forename: R
authors.initials: R
authors.lastname: Mallamaci
authors.forename: G S
authors.initials: GS
authors.lastname: Brigiani
authors.forename: R
authors.initials: R
authors.lastname: Capriulo
authors.forename: G
authors.initials: G
authors.lastname: Santoro
authors.forename: D C
authors.initials: DC
authors.lastname: Camerino
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007008:Hypokalemia / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010243:Paralysis / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel