Activation of Connexin-43 Hemichannels Can Elevate [Ca2+]iand [Na+]iin Rabbit Ventricular Myocytes During Metabolic Inhibition

Role of Inositol-1,4,5-Trisphosphate Receptor in the Regulation of Calcium Transients in Neonatal Rat Ventricular Myocytes

“…5A). Therefore, this observa- tion is in agreement with the finding in adult ventricle (13,17) and implies a potential interaction between Cx43 and IP 3 Rs. Furthermore, we examined whether Cx43 expression was affected by IP 3 R activation or interference using western blotting.…”

“…Thus, the above data showed that the formation of gap junctions may affect the behavior of Ca 2+ transients in NRVMs (13,17), and activation of IP 3 Rs can robustly enhance the frequency of endogenous spontaneous Ca 2+ transients in NRVMs, with or without gap junction channel formation. 2+ transient to baseline) as indicated were obtained from 53 and 67 cells in 6 independent determinations for single and monolayer NRVMs, respectively.…”

Connexin 43 Hemichannels and Pharmacotherapy of Myocardial Ischemia Injury

“…In fact, in the first study of Hc opening, which was conducted in Xenopus oocytes expressing Cx46, non-selective inward current, swelling, and cell death were observed (Paul et al, 1991). Subsequently, the opening of CxHc and consequent cell death following an ischemic insult were reported in different cell models including myocytes (Kondo et al, 2000;Li et al, 2001;Shintani-Ishida et al, 2007), astrocytes (Contreras et al, 2002;John et al, 1999a;John et al, 1999b), and renal tubule cells (Vergara et al, 2003). The involvement of Cx43Hc was also reported in cell lines, such HEK293 (John et al, 1999b) and HeLa (Contreras et al, 2002) cells, transfected with Cx43 that became more susceptible to death by simulated ischemia than non-transfected cells, a difference ascribable to Cx43Hc opening.…”

“…2) (Contreras et al, 2002). While Cx43 is phosphorylated under physiological conditions van Veen et al, 2001) and remains so in the first few minutes of ischemia , subsequent dephosphorylation of Cx43 occurs with increasing duration of myocardial ischemia (Beardslee et al, 2000;Jain et al, 2003;Jeyaraman et al, 2003;Miura et al, 2004;Schulz et al, 2003) a process that has been associated with the opening of unapposed Cx43Hc (John et al, 1999b;Li et al, 2001) which results in metabolic stress and cell death. Based on single Hc conductance measurements, it was suggested that opening of only 50 Hc is sufficient to drown the cell with Na + (John et al, 1999b).…”

“…However, under ischemic stress, the amount of non-phosphorylated Cx43 increases (Beardslee et al, 2000). Phosphorylation causes the unapposed Cx43Hc to close whereas, conversely, Cx43 dephosphorylation increases Hc conductance and permeability (Bao et al, 2007;Contreras et al, 2002;John et al, 1999b;Kondo et al, 2000;Li et al, 2001), an effect that can result in abnormal elevation of intracellular sodium and calcium loads (Li et al, 2001), release of ATP (Braet et al, 2003a;Braet et al, 2003b;Contreras et al, 2002), osmotic imbalance (John et al, 1999b;Li et al, 2001;Quist et al, 2000), swelling of myocytes Steenbergen et al, 1985;Tranum-Jensen et al, 1981) and lead to irreversible tissue injury (Shintani-Ishida et al, 2007) and cell death. Several kinases are involved in Cx43 phosphorylation (Cottrell et al, 2003;Duncan & Fletcher, 2002;Shi et al, 2001;TenBroek et al, 2001;Warn-Cramer et al, 1998), including protein kinase C (PKC) .…”