Characterization of Perturbing Actions by Verteporfin, a Benzoporphyrin Photosensitizer, on Membrane Ionic Currents

Mei-Han Huang; Ping-Yen Liu; Sheng-Nan Wu

doi:10.3389/fchem.2019.00566

Characterization of Perturbing Actions by Verteporfin, a Benzoporphyrin Photosensitizer, on Membrane Ionic Currents

Front Chem. 2019 Aug 22:7:566. doi: 10.3389/fchem.2019.00566. eCollection 2019.

Authors

Mei-Han Huang¹, Ping-Yen Liu², Sheng-Nan Wu^{3

4}

Affiliations

¹ College of Medical and Health Sciences, Fooyin University, Kaohsiung City, Taiwan.
² Division of Cardiovascular Medicine, National Cheng Kung University Medical College, Tainan City, Taiwan.
³ Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City, Taiwan.
⁴ Department of Physiology, National Cheng Kung University Medical College, Tainan City, Taiwan.

Abstract

Verteporfin (VP), a benzoporphyrin derivative, has been clinically tailored as a photosensitizer and recently known to suppress YAP-TEAD complex accompanied by suppression of the growth in an array of neoplastic cells. However, the detailed information is little available regarding possible modifications of it and its related compounds on transmembrane ionic currents, despite its growing use in clinical settings. In this study, from whole cell recordings, VP (0.3-100 μM) increased the amplitude of Ca²⁺-activated K⁺ currents (I _K(Ca)) in pituitary tumor (GH₃) cells in a concentration-dependent manner with an EC₅₀ value of 2.4 μM. VP-stimulated I _K(Ca) in these cells was suppressed by further addition of either paxilline, iberiotoxin, or dithiothreitol, but not by that of tobultamide or TRAM-39. VP at a concentration of 10 μM mildly suppressed the amplitude of delayed-rectifier K⁺ current; however, it had minimal effects on M-type K⁺ current. In cell-attached current recordings, addition of VP to the recording medium enhanced the activity of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels. In the presence of VP, additional illumination with light intensity of 5.5 mW/cm² raised the probability of BK_Ca-channel openings further. Addition of VP decreased the peak amplitude of L-type Ca²⁺ current together with slowed inactivation time course of the current; however, it failed to modify voltage-gated Na⁺ current. Illumination of GH₃ cells in continued presence of VP also induced a non-selective cation current. Additionally, VP increased the activity of BK_Ca channels in human 13-06-MG glioma cells with an EC₅₀ value of 1.9 μM. Therefore, the effects of VP on ionic currents described herein tend to be upstream of its inhibition of YAP-TEAD complex and they are conceivably likely to contribute to the underlying mechanisms through which it and its structurally similar compounds effect the modifications in functional activities of pituitary or glial neoplastic cells, if the in vivo findings occur.

Keywords: BKCa channel; Ca2+ current; Ca2+-activated K+ current; K+ current; glioma cell; pituitary tumor cell; verteporfin.