Modification of the cardiac action potential by intracellular injection of adenosine triphosphate and related substances in guinea pig single ventricular cells.

Abstract

SUMMARY. Effects of varying the intracellular adenosine triphosphate level on both the action potential and the membrane current were studied in single ventricular cells isolated from the guinea pig heart, using collagenase. Intracellular injection of adenosine triphosphate elevated the plateau potential level and prolonged the action potential duration. Similar results were obtained by injecting adenosine diphosphate, adenosine monophosphate, or creatine phosphate, i.e., substances considered to increase the intracellular concentration of adenosine triphosphate. In contrast, the action potential was depressed by procedures which could reduce the intracellular adenosine triphosphate level, such as an injection of creatine, superfusion of glucose-free Tyrode's solution containing 5.4 mM cyanide ion, or an injection of adenosine monophosphate into the cyanide-superfused cell. When the membrane current was recorded under the voltage clamp, it was found that the injection of adenosine triphosphate increased the amplitude of the slow inward current, whereas the superfusion of cyanide ion did not significantly decrease the slow inward current, although the action potential became considerably shorter. It was also found that the adenosine monophosphate injection decreased the amplitude of the net outward membrane current at the plateau level and increased it at around -40 mV,and thus intensified the N-shape of the isochronal 0.3-second current-voltage curve. The cyanide ion superfusion produced the opposite effect; in response to depolarizing clamp pulses more positive to the plateau level, the membrane current increased significantly with cyanide ion, but increased only slightly with adenosine triphosphate. These results suggest that intracellular adenosine triphosphate modifies the membrane currents at the plateau potential range, thus altering the action potential duration. (CircRes 53: 131-139, 1983)

Electrophysiological effects of adenosine and adenosine triphosphate on sheep Purkinje fibres under normal and simulated ischaemic conditions

“…Thus ATP, given extracellularly, is unable to protect against the abbreviation of the action potential that is, in part, induced by hypoxia (D. Pacini, unpublished work). Since it has been shown that intracellular injection of ATP does attenuate the action potential shortening caused by metabolic inhibitors (Taniguchi et al, 1983), it is most likely that our results reflect the rapid breakdown of ATP and lack of uptake into the cytoplasm.…”

Tolerance for ATP-Insensitive K ATP Channels in Transgenic Mice

“…Many studies have demonstrated that a fall of intracellular [ATP] is likely to be a major determinant of K ATP channel opening when metabolism is inhibited. 22,23,44 Quantitative models of cardiac action potentials, incorporating experimentally measured K ATP properties, indicate that relatively small decreases of [ATP] within the millimolar range, coupled with an increase of [ADP] under such conditions, are likely to result in marked action potential shortening [25][26][27][28] if ATP sensitivity is reduced by as little as 4-fold (not shown). The use of a hyperpolarizing holding current will cause a variable reduction of the APD, precluding detailed analysis of action potential waveforms.…”

Electrophysiology of single cardiac cells.

“…The sample and hold type voltage clamp experiments using one microelectrode [21,40,62,63] as well as two microelectrodes were made [3,32,40]. Using the latter method, the activation and inactivation time courses of the calcium current have been much improved [59]. The second electrode was a large suction electrode (diameter 5 to 8 um) [33] which was initially developed for the study of the Aplysia ganglion cell; later it was applied to heart cells [2,3,18,34,35].…”

“…Also, it is possible that some unknown property of the membrane may be lost after enzymatic treatment. been modified [59], but others [2,3,6,49,50] did not use that solution. BUSTAMANTE et al [6] also perfused with the collagenase solution for only 10 min and prepared the specimen in a straightforward way.…”