Long-term impact of frailty on mortality and quality of life in mechanically ventilated acute myocardial infarction patients undergoing percutaneous coronary intervention.

Bis-(1,2,3,4-tetrahydroisoquinoline) derivatives (Bis-THIQ) represent a promising class of natural alkaloids in terms of their biological and therapeutic potential [,]. The affinities of two compounds from this class, cepharanthine and oxyacanthine (), for small-conductance calcium-activated potassium (SK) channel subtypes were recently reported by our group []. SK channels are voltage-independent membrane proteins that open in response to increases in intracellular Ca concentration. Although they are K ion permeable, their conductance is lower than that of other potassium channel types. These characteristics make them ideal candidates for regulating several physiological mechanisms. Primarily, they modulate neuronal firing rate by contributing to the AfterHyperPolarization (AHP) phase of the neuronal refractory period []. Peripherally, they are also expressed in the cardiac atria, where they are involved in heart rate regulation []. Thus, various tissues can differentially express one or more of the three known SK channel subtypes: SK1 (K2.1), SK2 (K2.2) or SK3 (K2.3) (encoded by , and genes, respectively). SK channel subtypes are implicated in numerous pathologies, often with a specific mechanism linked to a single subtype. Prominent examples include depression and other mood disorders, where SK3 channels are upregulated in serotonin-producing neurons of the basal nuclei [,], and atrial fibrillation, which is associated with SK2 overexpression in atrial cardiomyocytes []. Both subtypes are also upregulated during the progression of various cancers [,]. Specifically, the SK2 subtype is expressed under hypoxic conditions, such as in melanomas [], whereas the SK3 subtype drives the mobility of several cancer cell types, including invasive breast cancer [].