Modulatory effects of myomodulin on the excitability and membrane currents in Retzius cells of the leech.

Abstract

Ion channel modulation by the peptide myomodulin (MM) has been demonstrated in a wide variety of organisms including Aplysia, Lymnaea, and Pleurobranchaea. This neural and muscular modulation has been shown to be important for shaping and modifying behavior. In this paper, we report that MM modulates several distinct ionic channels in another species, the medicinal leech Hirudo medicinalis. Experiments have focused on the Retzius cell (R) because the R cell is a multifunction neuron that has been implicated in a number of behaviors including feeding, swimming, secretion, thermal sensing, and the touch elicited shortening reflex and its plasticity. Previous work had identified a MM-like peptide in the leech and demonstrated that this peptide modulated the excitability of the R cell. Using combined current- and voltage-clamp techniques to examine the effects of MM on the R cell, we found that in response to a step pulse, MM increased the excitability of the R cell such that the cell fires more action potentials with a shorter latency to the first action potential. We found that this effect was mediated by the activation of a Na+-mediated inward current near the cell resting membrane potential. Second, we found that MM differentially modulated the potassium currents IA and IK. No effect of MM was found on IA, whereas MM significantly reduced both the peak and steady-state amplitudes of IK by 49 +/- 2.9% and 43 +/- 7.2%, respectively (means +/- SE). Finally we found that MM reduced the amplitude of the Ca2+ current by approximately 20%. The ionic currents modulated by MM are consistent with the overall effect of MM on the cellular activity of the R cell. An understanding of the cellular mechanisms by which MM modulates the activity of the R cell should help us to better understand the roles of both MM and the R cell in a variety of behaviors in the leech.