Insensitivity of the open state of (-)-DPI-modified cardiac Na+ channels to the blocking effects of the (+) enantiomer.
Elementary Na+ currents in DPI-modified cardiac Na+ channels were recorded in the absence and presence of the blocking (+) enantiomer in inside-out patches from cultured neonatal rat cardiocytes. After external application of (-)-DPI (3 mumols/l), the kinetics of modified, non-inactivating Na+ channels were found to be indistinguishable from the channel kinetics observed in the presence of (+/-)-DPI (6 mumols/l). The open state and burst duration proved insensitive to the blocking (+) enantiomer in concentrations up to 3 mumols/l. At -30 mV, the exit rates from the open and the bursting state were 105 +/- 11 and 57 +/- 6 s-1, respectively, with (-)-DPI or 88 +/- 6 and 49 +/- 8 s-1, respectively, with (+/-)-DPI. The use of (+/-)-DPI 201-106 as a pharmacological modifier of channels will, therefore, provide reliable kinetic data of non-inactivating Na+ channels.
Kohlhardt
M
M
Physiological Institute, University Freiburg, F.R.G.
D000818:Animals; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism
D010879:Piperazines; D015222:Sodium Channels; C046261:DPI 201-106