Identification of two types of ATP-sensitive K+ channels in rat ventricular myocytes.
The ATP-sensitive K(+) (K(ATP)) channels are known to provide a functional linkage between the electrical activity of the cell membrane and metabolism. Two types of inwardly rectifying K(+) channel subunits (i.e., Kir6.1 and Kir6.2) with which sulfonylurea receptors are associated were reported to constitute the K(ATP) channels. In this study, we provide evidence to show two types of K(ATP) channels with different biophysical properties functionally expressed in isolated rat ventricular myocytes. Using patch-clamp technique, we found that single-channel conductance for the different two types of K(ATP) channels in these cells was 57 and 21 pS. The kinetic properties, including mean open time and bursting kinetics, did not differ between these two types of K(ATP) channels. Diazoxide only activated the small-conductance K(ATP) channel, while pinacidil and dinitrophenol stimulated both channels. Both of these K(ATP) channels were sensitive to block by glibenclamide. Additionally, western blotting, immunochemistry, and RT-PCR revealed two types of Kir6.X channels, i.e., Kir6.1 and Kir6.2, in rat ventricular myocytes. Single-cell Ca(2+) imaging also revealed that similar to dinitrophenol, diazoxide reduced the concentration of intracellular Ca(2+). The present results suggest that these two types of K(ATP) channels may functionally be related to the activity of heart cells.
Wu
Sheng-Nan
SN
Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan. snwu@mail.ncku.edu.tw
Wu
Adonis Z
AZ
Sung
Ruey J
RJ
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019085:Fluorescent Antibody Technique, Direct; D015870:Gene Expression / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099161:Kcnj11 Channel
D002118:Calcium; D003981:Diazoxide; D004140:Dinitrophenols; D005905:Glyburide; D054086:KATP Channels; D020110:Pinacidil; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel