Role of Ca²⁺ and ion channels in the regulation of apoptosis under hypoxia

Miaohong Wang¹, Jin Tan¹, Yuyang Miao², Mengmeng Li¹ and Qiang Zhang<sup>1

1</sup>Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute and ²Tianjin Medical University, Tianjin, China

Offprint requests to: Qiang Zhang, Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, NO.154 Anshan Road, Heping District, Tianjin 300052, China. e-mail: zhangqiangyulv@163.com

Summary. Hypoxia is a kind of common pathological condition existing in various diseases such as sleep apnea syndrome, myocardial infarction and stroke, which can precipitate the onset of diseases through inducing cell apoptosis. Ca²⁺ is the ubiquitous message in cell. Given the crucial role of Ca²⁺ in physiology, intracellular Ca²⁺ overload is a significant regulator of apoptosis. Numerous experiments show that hypoxia may cause changes of multiple cellular Ca²⁺ channels, for instance, Na⁺/Ca²⁺ Exchanger (NCX), L-type voltage dependent Ca²⁺ channel (L-VDCC), inositol triphosphate receptors (IP3R) and so on, which contribute to intracellular Ca²⁺ overload, thus eventually triggering cell apoptosis. However, the mechanisms underlying different Ca²⁺ channels involved in hypoxic apoptosis are complex. For example, chronic hypoxia or acute hypoxia may select different Ca²⁺ channels to influence cell apoptosis. In addition, intracellular Ca²⁺ overload may initiate different apoptotic pathways due to hypoxic duration. Furthermore, different locations in the cell of specific Ca²⁺ channels activated by hypoxia will determine different apoptosis signaling pathways. Moreover, activation of different Ca²⁺ channel isoforms will result in different outcomes of the cell under hypoxia. Hence, we aim to highlight the potential mechanisms of the main Ca²⁺ channels in regulation of apoptosis under hypoxic stress. Histol Histopathol 33, 237-246 (2018)

Key words: Hypoxia, Apoptosis, Ca²⁺, Ca²⁺ channels

DOI: 10.14670/HH-11-918