ATP-sensitive potassium (KATP) chan

ATP-sensitive potassium (KATP) channels sit at the crossroads of cell metabolism and membrane excitability. These members of the family of inwardly rectifying K1 channels are activated by Mg21-ound nucleotides and inhibited by intracellular ATP (1). Thus, KATP channels are open during states of
low metabolic activity, resulting in hyperpolarization of the membrane, which has cytoprotective effects in vascular and neural tissues (2, 3). In high metabolism, KATP channel activity decreases and the resulting membrane depolarization triggers cellular responses such as insulin secretion (4). First described in ventricular myocytes (5, 6), KATP channels have been found in tissues throughout the body, including pancreatic b-cells (7), skeletal muscle (8), visceral and vascular smooth muscle (9), and brain (10, 11). Although roles in glucose homeostasis and ischemic protection are well established (12–14), novel functions of KATP channels continue to emerge: recognized as protective against neural apoptosis following a stroke (3), brain KATP channels have recently been implicated in memory (15) and in the regulation of male reproductive behavior (16). Mutations leading to absent, decreased, or hyperactive KATP channels have been linked to a variety of diseases, from mild and transient to severe and permanent neonatal diabetes (17–19), and efforts continue to be made to understand the implications of KATP channels in health and disease. Classic KATP channel openers, such as diazoxide and pinacidil, have been used to treat hypertension, angina, and hyperinsulinism of infancy, while antagonists such as sulfonylureas are established antidiabetic agents (20). The drug industry continues to exploit the tissue specific pharmacology of KATP channels in the design of novel therapeutic agents aimed at endocrine, vascular, neurological, urological, and even dermatological ailments (21). Here, we will summarize current understanding of the molecular biology, pharmacology, and physiology of KATP channels and the disease states that result from aberrant expression or function of these proteins, with a special focus on the pancreas and the cardiovascular system.

Hasil (Bahasa Indonesia) 1:

ATP-sensitif kalium (KATP) saluran duduk di persimpangan sel metabolisme dan membran Involuntary. Ini anggota dari keluarga dalam hati meluruskan K1 saluran diaktifkan oleh nukleotida Mg21-ound dan dihambat oleh intraseluler ATP (1). Dengan demikian, KATP saluran terbuka selama Serikatlow metabolic activity, resulting in hyperpolarization of the membrane, which has cytoprotective effects in vascular and neural tissues (2, 3). In high metabolism, KATP channel activity decreases and the resulting membrane depolarization triggers cellular responses such as insulin secretion (4). First described in ventricular myocytes (5, 6), KATP channels have been found in tissues throughout the body, including pancreatic b-cells (7), skeletal muscle (8), visceral and vascular smooth muscle (9), and brain (10, 11). Although roles in glucose homeostasis and ischemic protection are well established (12–14), novel functions of KATP channels continue to emerge: recognized as protective against neural apoptosis following a stroke (3), brain KATP channels have recently been implicated in memory (15) and in the regulation of male reproductive behavior (16). Mutations leading to absent, decreased, or hyperactive KATP channels have been linked to a variety of diseases, from mild and transient to severe and permanent neonatal diabetes (17–19), and efforts continue to be made to understand the implications of KATP channels in health and disease. Classic KATP channel openers, such as diazoxide and pinacidil, have been used to treat hypertension, angina, and hyperinsulinism of infancy, while antagonists such as sulfonylureas are established antidiabetic agents (20). The drug industry continues to exploit the tissue specific pharmacology of KATP channels in the design of novel therapeutic agents aimed at endocrine, vascular, neurological, urological, and even dermatological ailments (21). Here, we will summarize current understanding of the molecular biology, pharmacology, and physiology of KATP channels and the disease states that result from aberrant expression or function of these proteins, with a special focus on the pancreas and the cardiovascular system.

Hasil (Bahasa Indonesia) 2:

ATP-sensitif kalium (KATP) saluran duduk di persimpangan metabolisme sel dan rangsangan membran. Anggota-anggota keluarga dari dalam hati meluruskan saluran K1 diaktifkan oleh nukleotida Mg21-ound dan dihambat oleh intraseluler ATP (1). Dengan demikian, saluran KATP terbuka selama keadaan
aktivitas metabolik yang rendah, mengakibatkan hiperpolarisasi membran, yang memiliki efek sitoprotektif di pembuluh darah dan jaringan saraf (2, 3). Dalam metabolisme tinggi, KATP aktivitas saluran menurun dan depolarisasi membran yang dihasilkan memicu respon seluler seperti sekresi insulin (4). Pertama kali dijelaskan pada miosit ventrikel (5, 6), saluran KATP telah ditemukan di seluruh jaringan tubuh, termasuk b-sel pankreas (7), otot skeletal (8), visceral dan otot polos pembuluh darah (9), dan otak (10 , 11). Meskipun peran dalam homeostasis glukosa dan perlindungan iskemik mapan (12-14), fungsi novel saluran KATP terus bermunculan: diakui sebagai pelindung terhadap apoptosis neural menyusul stroke (3), saluran KATP otak baru-baru ini terlibat dalam memori (15 ) dan dalam regulasi perilaku reproduksi laki-laki (16). Mutasi yang menyebabkan absen, menurun, atau saluran KATP hiperaktif telah dikaitkan dengan berbagai penyakit, dari ringan dan sementara diabetes neonatal parah dan permanen (17-19), dan upaya terus dilakukan untuk memahami implikasi dari saluran KATP di kesehatan dan penyakit. Klasik KATP saluran pembuka, seperti diazoxide dan pinacidil, telah digunakan untuk mengobati hipertensi, angina, dan hiperinsulinisme dari masa bayi, sedangkan antagonis seperti sulfonilurea ditetapkan agen antidiabetes (20). Industri obat terus mengeksploitasi farmakologi spesifik jaringan saluran KATP dalam desain agen terapi baru yang bertujuan endokrin, pembuluh darah, saraf, urologi, dan penyakit bahkan dermatologis (21). Di sini, kita akan merangkum pemahaman saat ini molekul biologi, farmakologi, dan fisiologi saluran KATP dan negara-negara penyakit yang dihasilkan dari ekspresi menyimpang atau fungsi protein tersebut, dengan fokus khusus pada pankreas dan sistem kardiovaskular.