Abstract
The ionic mechanisms controlling the resting membrane potential (RMP) in superior cervical ganglion (SCG) neurons have been widely studied and the M-current (IM, KCNQ) is one of the key players. Recently, with the discovery of the presence of functional TREK-2 (TWIK-related K+ channel 2) channels in SCG neurons, another potential main contributor for setting the value of the resting membrane potential has appeared. In the present work, we quantified the contribution of TREK-2 channels to the resting membrane potential at physiological temperature and studied its role in excitability using patch-clamp techniques. In the process we have discovered that TREK-2 channels are sensitive to the classic M-current blockers linopirdine and XE991 (IC50 = 0.310 ± 0.06 µM and 0.044 ± 0.013 µM, respectively). An increase from room temperature (23 °C) to physiological temperature (37 °C) enhanced both IM and TREK-2 currents. Likewise, inhibition of IM by tetraethylammonium (TEA) and TREK-2 current by XE991 depolarized the RMP at room and physiological temperatures. Temperature rise also enhanced adaptation in SCG neurons which was reduced due to TREK-2 and IM inhibition by XE991 application. In summary, TREK-2 and M currents contribute to the resting membrane potential and excitability at room and physiological temperature in the primary culture of mouse SCG neurons.
Highlights
Superior cervical ganglion neurons (SCG) have been used as a model to study the resting membrane potential (RMP) and excitability [1,2]
We decided to demonstrate that traditional M-current blockers, linopirdine and XE991, did not affect the TREK-2 current activated by riluzole (IRIL) [6]
We found that both substances strongly inhibited IRIL, in mouse superior cervical ganglion neurons (SCG) neurons (TREK-2 native current) and in a HEK293 cell line (TREK-2 expressed currents)
Summary
Superior cervical ganglion neurons (SCG) have been used as a model to study the resting membrane potential (RMP) and excitability [1,2]. The RMP in rodent sympathetic neurons is sustained around −60 mV thanks to the contribution of voltage-dependent and independent currents. Considering the voltage-dependent currents, the main contributors to the RMP in SCG neurons are the potassium M-current (IM), the cationic h-current (Ih) and a sodium persistent current (INaP). IM tends to hyperpolarize while Ih tends to depolarize the membrane potential in a similar amount (≈7 mV), having a strong stabilizing effect on the RMP [4]. The voltage independent currents involved in maintaining the RMP in SCG neurons are carried by the Na/K pump (leak-like) and by two pore domain potassium channels (K2P), both of them contributing a hyperpolarizing factor [4,6]
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