Cation‐dependent gating of the hyperpolarization‐activated cation current in the rabbit sino‐atrial node cells.

Abstract

1. The gating properties of the hyperpolarization-activated cation current (If or either by prolonging the duration or by increasing the amplitude of the preceding hyperpolarization in both Na+ and Li' solutions.5. The If was first activated by hyperpolarizing the membrane to -110 mV, and then deactivated by depolarization. The inward tail current at -50 mV showed a single exponential decay. At more positive potentials, the shoulder of the outward tail currents became more evident and the rate of the final decay was increased.6. The time course of If activation was well fitted with the sum of two exponential functions. Time constants of both components were not affected by the external cation (Na+, K' or Li') replacement. Likewise, the quasi-steady state activation was conserved when external Na+ was replaced with Li'. 7. Two closed and three open states were assumed in a sequential state model of the If channel. The cation effects were well simulated by assuming that the deactivation rate was selectively modulated. The flow of If during the spontaneous action potential was calculated. The activation of If started on repolarization to the maximum diastolic potential and reached a maximum in the middle of the diastolic period. Its peak amplitude was 14 % of the net inward current during the diastolic period.

Separable Gating Mechanisms in a Mammalian Pacemaker Channel

“…Extrapolation of the measured I f values yielded an x-intercept of 0.21 indicating that I f was eliminated despite the fact that driving forces were inward for both Na ϩ and K ϩ . This behavior has also been reported in studies of native I f (8,(27)(28)(29). The corresponding concentrations determined at the x-intercept were 3.3 mM K ϩ and 136.7 mM Na ϩ , which compares to 3.8 mM K ϩ and 136.3 mM Na ϩ determined at Ϫ65 mV (Fig.…”

“…Previous studies of I f in sensory neurons, apical dendrites of hippocampal CA1 pyramidal neurons, and myocytes from the sinoatrial node have shown that deactivation was affected by relatively large changes in external cations (28,40,41). Despite concurrent changes in I f amplitude that reflected interactions of Na ϩ and K ϩ in the pore, a separate mechanism was proposed for the effects of cations on I f deactivation that involve an external binding site (28). The primary argument in favor of an external binding site was that only K ϩ could be present in the pore during measurements of outward tail currents because Na ϩ was not present in the intracellular solution and thus would have left the pore almost instantly upon depolarization.…”

Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis

“…The intriguingly similar activation kinetics of I f in myocytes of the sinoatrial node and cardiac Purkinje fibers (28)(29)(30) and of hHCN4 certainly support this conclusion. However, the activation threshold of I f in cardiac Purkinje fiber is distinctively more negative than in the sinoatrial node (29,31).…”

Bidirectional Interactions between H-Channels and Na+–K+Pumps in Mesencephalic Trigeminal Neurons

“…ϩ is permeant through h-channels (Ho et al, 1994;Maruoka et al, 1994) but does not stimulate the Na ϩ -K ϩ pump as strongly as Na ϩ ions (Foley, 1984;Chen et al, 1989;Rasmussen et al, 1989). As shown in Figure 6 Aa, when extracellular Na ϩ ions were substituted with Li ϩ ions, the apparent I h was depressed or enhanced depending on the amplitude of test pulses applied at Ϫ50 mV (n ϭ 5).…”