Novel voltage-dependent non-selective cation conductance in murine colonic myocytes

摘要

class="enumerated" style="list-style-type:decimal">Two components of voltage-gated, inward currents were observed from murine colonic myocytes. One component had properties of L-type Ca²⁺ currents and was inhibited by nicardipine (5 × 10⁻⁷m). A second component did not ‘run down’ during dialysis and was resistant to nicardipine (up to 10⁻⁶m). The nicardipine-insensitive current was activated by small depolarizations above the holding potential and reversed near 0 mV.This low-voltage-activated current (ILVA) was resolved with step depolarizations positive to −60 mV, and the current rapidly inactivated upon sustained depolarization. The voltage of half-inactivation was −65 mV. Inactivation and activation time constants at −45 mV were 86 and 15 ms, respectively. The half-recovery time from inactivation was 98 ms at −45 mV. ILVA peaked at −40 mV and the current reversed at 0 mV.Ilva was inhibited by Ni²⁺ (IC50= 1.4 × 10⁻⁵m), mibefradil (10⁻⁶ to 10⁻⁵m), and extracellular Ba²⁺. Replacement of extracellular Na⁺ with N-methyl-d-glucamine inhibited ILVA and shifted the reversal potential to -7 mV. Increasing extracellular Ca²⁺ (5 × 10⁻³m) increased the amplitude of ILVA and shifted the reversal potential to +22 mV. ILVA was also blocked by extracellular Cs⁺ (10⁻⁴m) and Gd³⁺ (10⁻⁶m).Warming increased the rates of activation and deactivation without affecting the amplitude of the peak current.We conclude that the second component of voltage-dependent inward current in murine colonic myocytes is not a ‘T-type’ Ca²⁺ current but rather a novel, voltage-gated non-selective cation current. Activation of this current could be important in the recovery of membrane potential following inhibitory junction potentials in gastrointestinal smooth muscle or in mediating responses to agonists.