Tetraethylammonium (TEA) increases the inactivation time constant of the transient K⁺ current in suprachiasmatic nucleus neurons

Identifying the mechanisms that drive suprachiasmatic nucleus (SCN) neurons to fire action potentials with a higher frequency during the day than during the night is an important goal of circadian neurobiology. Selective chemical tools with defined mechanisms of action on specific ion channels are required for successful completion of these studies. The transient K⁺ current (I_A) plays an active role in neuronal action potential firing and may contribute to modulating the circadian firing frequency. Tetraethylammonium (TEA) is frequently used to inhibit delayed rectifier K⁺ currents (I_DR) during electrophysiological recordings of I_A. Depolarizing voltage-clamped hamster SCN neurons from a hyperpolarized holding potential activated both I_A and I_DR. Holding the membrane potential at depolarized values inactivated I_A and only the I_DR was activated during a voltage step. The identity of I_A was confirmed by applying 4-aminopyridine (5 mM), which significantly inhibited I_A. Reducing the TEA concentration from 40 mM to 1 mM significantly decreased the I_A inactivation time constant (τ_inact) from 9.8 ± 3.0 ms to 4.9 ± 1.2 ms. The changes in I_A τ_inact were unlikely to be due to a surface charge effect. The I_A amplitude was not affected by TEA at any concentration or membrane potential. The isosmotic replacement of NaCl with choline chloride had no effect in I_A kinetics demonstrating that the TEA effects were not due to a reduction of extracellular NaCl. We conclude that TEA modulates, in a concentration dependent manner, τ_inact but not I_A amplitude in hamster SCN neurons.