RESUMO
Aim To study the characteristics of KCNQ2/3 potassium channel expressed in CHO cells and its modulation by M_1 receptor.Methods KCNQ2 and KCNQ3 potassium channels and M_1 receptor were co-expressed in CHO cells.Whole cell patch-clamp techniques was used to observe the characteristics of KCNQ2/3 current,its modulation by the M_1 receptor,and the effects of the common potassium channel blockers.Results KCNQ2/3 current recorded in CHO cells was a slow-activation low-threshold non-inactivating,voltage-dependent outward potassium current.KCNQ2/3 current was elicited at about-60 mV,V_(1/2)(-26.8?1.2) mV and the deactivation current fitted two exponential function,with ?_(fast) of 101ms and ?_(slow) of 309 ms.The channel was not sensitive to common pharmacological blockers such as 4-AP,Ba~(2+) and TEA,but was inhibited significantly by linopirdine,with a IC_(50) of(6.5?0.83) ?mol?L~(-1).Acetylcholine suppressed the KCNQ2/3 current reversibly via M_1 receptor,with a IC_(50) of(0.7?0.05) ?mol?L~(-1).Conclusion KCNQ2 and KCNQ3 channels are the molecular basis of M-current observed in neuronal cells.KCNQ2/Q3 current expressed in CHO cells has similar characteristics as that seen in neuronal M-current.Linopirdine is a powerful blocker of KCNQ2/3 channel and acetylcholine inhibits the current by muscarinic M_1 receptor.This experiment has laid a solid basis for further study of M-current and KCNQ2/3 current,and is important for the study of neurological diseases relating to alteration of M-current,such as convulsion,epilepsy and Alzheimers disease.
RESUMO
KCNQ channels are an important sub-family in potassium channels. They are divided into five subtypes, including KCNQ1, KCNQ2, KCNQ3, KCNQ4, KCNQ5. KCNQ channels have a wide range of physiological and pathophysiologi-cal correlates. KCNQ1 (KvLTQ1) forms cardiac-delayed rectifier-like K+ current in the heart with other subunits. Mutations in this channel can cause one form of inherited long QT syndrome (LQT1). KCNQ2 and KCNQ3 heteromultimers are thought to underlie the M-current; mutations in these genes may cause an inherited form of juvenile epilepsy. The KCNQ4 gene is thought to encode the molecular correlate of the 7K.n in outer hair cells of the cochlea mutations whose mutation leads to a form of inherited deafness. KCNQ5 co-assemble with KCNQ3 in brain, and may also play a role in the M-current heterogeneity.
RESUMO
M channel, a voltage-dependent potassium channel, has been found in a variety of neurons. It is activated near the threshold of neuron action potential,producing a primary K~+ current, namely the M-current. The M-current can be modulated by many neurotransmitters and hormones, which can influence neuron excitability, conduction and neurotransmitter release. This review discusses the signal transduction pathway from G_~ q/11 activation to intracellular calcium, membrane phospholipid and phosphokinase, and explains the mechanism of M-current modulation by neurotransmitters.