Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches

Abstract

Inward rectifying potassium single-channel currents were studied in the membrane of guinea pig cardiac myocytes. In isolated inside-out patches two different channels were observed: a channel of 25 pS conductance ([K+]o = 147 mM, T = 21 degrees C), if the solution at the cytoplasmic face of the patch contained 4 mM ATP and a channel of 80 pS conductance without ATP. The 25-pS-channel was also regularly seen in cell-attached patches (Sakmann and Trube 1984a,b), but the 80-pS-channel appeared only after inhibiting cellular metabolism by DNP. The percentage of time which the 25-pS-channel spent in the open state was 3.3 times larger in isolated patches compared to cell-attached patches. However, both types of single channel currents disappeared several minutes after the isolation of the patches. In contrast to the 25-pS-channel, the 80-pS-channel, which is activated by the lack of ATP, carried measurable outward currents saturating at 1.5 pA (inward rectification). It is suggested that the 80-pS-channel mediates part of the increase in potassium current during metabolic inhibition. The openings of this channel appeared in bursts. The mean open time was 1.6 ms and the mean duration of the gaps within bursts 0.33 ms at -80 mV.

Two types of ATP‐sensitive potassium channels in rat portal vein smooth muscle cells

“…Free ATP and Mg-ATP were both effective with Mg-ATP slightly more efficient (Findlay, 1988;Lederer & Nichols, 1989 (Trube & Hescheler, 1984;Kakei et al, 1985) when external K concentration was about 50-70 mM. In the present experiments, the unitary conductance of the LK channel was 49 pS when external K concentration was 60 mM.…”

“…A most important property of KATP channels is dramatic channel open-ings in isolated patches in the absence of ATP (Noma, 1983;Trube & Hescheler, 1984;Ashcroft & Kakei, 1989; and potent inhibition of the KATP channel activity by ATP with the half-maximal inhibition (Kj) at about [17][18][19][20][21][22][23][24][25] gM in rat cardiac cells (Findlay, 1988;Lederer & Nichols, 1989) and 4 gM in rat pancreatic fl-cells (Ashcroft & Kakei, 1988). In smooth muscle, however, there is still much controversy about the existence of KATP channels and their properties.…”

ATP‐sensitive K+ channels in heart muscle cells first open and subsequently close at maintained anoxia

“…Since the discovery of KArp-channels in the myocardium [6,15] there has been an extensive debate as to whether or not these channels contribute to the extracellular accumulation of K ÷ during ischaemia. The main objections against a relevant contribution of KATp-channels are: (i) half maximum inhibition of the channel activity is reached at tens to hundreds of/aM ATP [16,17] whereas measured ATP levels in the ischaemic myocardium are in the range of several mM [18][19][20] which would allow only a few channels to open.…”

“…One possible mechanism underlying this K ~ accumulation is the opening of ATP-sensitive K ÷ channels (KArp-channels) which has been described to appear in isolated heart cells by application of inhibitors of the oxidative metabolism [5][6][7][8] or by anoxia [9]. The most likely opening mechanism is a sufficient drop of the cytosolic ATP (or the ATP/ADP ratio).…”

Effects of sulphonylureas and diazoxide on insulin secretion and nucleotide‐sensitive channels in an insulin‐secreting cell line

“…Another major class of K + selective channels present in B-cells Findlay et al, 1985) and this cell line (Sturgess et al, 1986a) (Findlay et al, 1985) and in cardiac (Trube & Hescheler, 1984) and skeletal (Spruce et al, 1987) An alternative method of assessing the concentration-dependence of these compounds is to use the whole-cell configuration (Trube et al, 1986). By allowing dialysis of the cell interior with the pipette solution (and washout of ATP), the overall (cellular) potassium conductance observed, under voltage clamp, is due to the increased activation of the ATP-K+ channel (Rorsman & Trube, 1985).…”