Thermodynamic properties of hyperpolarization-activated current (Ih) in a subgroup of primary sensory neurons

Abstract

Ih is a poorly selective cation current that activates upon hyperpolarization, present in various types of neurons. Our aim was to perform a detailed thermodynamic analysis of Ih gating kinetics, in order to assess putative structural changes associated with its activation and deactivation. To select dorsal root ganglia neurons that exhibit large Ih, we applied a current signature method by Petruska et al. (J Neurophysiol 84:2365-2379, 2000) and found appropriate neurons in cluster 4. Currents elicited by 3,000-ms hyperpolarizing pulses at 25 and 33 degrees C were fitted with double exponential functions, yielding time constants similar to those of HCN1. The fast activation and deactivation rates showed temperature coefficients (Q10) of 2.9 and 3.1, respectively, while Q10 of the absolute conductance was 1.3. Using the Arrhenius-Eyring formalism we computed heights of voltage-independent Gibbs free energy and entropy barriers for each rate. The free energy barriers of the fast rates were just approximately 2RT units lower than those of the corresponding slow rates (31.3 vs. 33.2RT for activation, and 24.7 vs. 25.8RT for deactivation, at 25 degrees C). Interestingly, the entropy barriers of the slow rates were negative: -15.2R units for activation and -11.9R units for deactivation, compared to 4.6 and 1.3R units, respectively, for the fast component. The equivalent gating charge (zg) (3.75 +/- 0.32, mean +/- SEM, at 25 degrees C) and half-activation potential (V1/2) (-70.0 +/- 1.3 mV at 25 degrees C) did not vary significantly with temperature.

Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs

“…I h is an inward (depolarizing) Na ϩ /K ϩ current carried by hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Consistent with evidence that cooling inhibits I h (11,37,40), we found cooling eliminated the depolarizing voltage "sag" caused by activation of I h during negative current injection (47). Inhibition of an excitatory membrane current associated with pacemaking is seemingly at odds with our findings that LC neurons intrinsically increase spontaneous discharge at cold temperatures.…”

The h-Current in the Substantia Nigra pars Compacta Neurons: A Re-examination

“…It has been shown in various types of preparation that the kinetics of I h is particularly sensitive to thermic conditions [20], [30], [31]. The temperature at which electrophysiological recordings are made, affecting both the amplitude and the kinetics of I h (Figure 4A), is one of the limiting factors in comparing the results; therefore, in this study most of the reported recordings were realized in precisely controlled temperature conditions.…”

“…These measurement errors are more pronounced for slow HCN channels than for the fast ones, and are highly dependent on temperature [19], [20]. Therefore, we have analyzed the dependence of the midpoint from the duration of the conditioning command.…”

Differential regulation of HCN channel isoform expression in thalamic neurons of epileptic and non-epileptic rat strains

“…For I h basal parameters were set as follows: ghbar_iar = 1e-5 S/cm 2 ; V h = −74.7 mV; maximum τ m value at −80 mV = 1010 ms. The Q 10 value of I h was set to 3 (Pena et al, 2006). The accuracy of the mathematical description of I h with respect to currents recorded at physiological temperature has been demonstrated before (Huguenard and McCormick, 1992).…”