Oscillatory activation of calcium-dependent potassium channels in HeLa cells induced by histamine H1 receptor stimulation: A single-channel study

Abstract

We have used the patch-clamp method (O.P. Hamill et al.,Pfluegers Arch.,391:85–100, 1981) in order to investigate the activation pattern of a calcium-dependent potassium channel following H₁ receptor stimulation in HeLa cells. Our results essentially indicate that the stimulation of H₁ receptors by exogenous histamine at concentrations greater than 1 μm induces an oscillatory activation pattern of calcium-dependent potassium channels characterized by the occurrence of channel current bursts separated by long silent periods. It was also found that the occurrence of these bursts could be directly correlated with transmembrane potential oscillations, the latter being the resulting effect of the calcium-dependent potassium channel synchronous openings. In addition, the cyclic activation of the calciumdependent potassium channels could be initiated by the addition of histamine to a calcium-free external medium, indicating that the stimulation of the H₁ receptors in HeLa cells is mainly related to the release of calcium from internal stores. Finally, the membrane-permeable cyclic AMP analog dibutyryl cyclic AMP was found to be ineffective in initiating single-channel events such as those triggered by exogenous histamine. It is proposed that the oscillatory activation of the calcium-dependent potassium channels in HeLa cells results from a repetitive transient increase in cytosolic free calcium concentration consequent to the H₁ receptor stimulation.