Understanding effects on excitability of simulated I (h) modulation in simple neuronal models

The hyperpolarization-activated, inward, mixed cation current, I (h), appears in a wide variety of cells in the nervous system, contributes to diverse neuronal properties, and is up-regulated by a number of important neurotransmitters. Up-regulation of I (h) is usually associated with an excitability-enhancing depolarization of resting membrane potential and an excitability-depressing shunting effect caused by a decrease in input resistance. In order to gain a better understanding of the interaction of these effects and their influence on excitability with I (h) modulation, we systematically analyze changes in neuronal properties associated with excitability during I (h) modulation in simplified, yet, biophysical neuron models based on a hippocampal pyramidal neuron. We simulate I (h) modulation by varying both its maximal conductance and its half-activation voltage, mimicking the effects of cAMP-linked neurotransmitters, through ranges of physiologically realistic parameter regimes. Of particular interest is the contribution of the different effects of I (h) up-regulation when membrane potentials are held at common levels and neuronal excitability is probed. Our modeling results suggest that, although holding potentials at common levels may compensate for changes in resting membrane potentials, this protocol may exaggerate the excitability-depressing influences of changes in input resistances with I (h) up-regulation.