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

Two components of voltage‐gated, inward currents were observed from murine colonic myocytes. One component had properties of L‐type Ca 2+ currents and was inhibited by nicardipine (5 × 10 −7 m ). A second component did not ‘run down’ during dialysis and was resistant to nicardipine (up to 10 −6 m ). The nicardipine‐insensitive current was activated by small depolarizations above the holding potential and reversed near 0 mV. This low‐voltage‐activated current ( I LVA ) 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. I LVA peaked at ‐40 mV and the current reversed at 0 mV.Ilvawas inhibited by Ni 2+ (IC 50 = 1.4 × 10 −5 m ), mibefradil (10 −6 to 10 −5 m ), and extracellular Ba 2+ . Replacement of extracellular Na + with N ‐methyl‐ d ‐glucamine inhibited I LVA and shifted the reversal potential to ‐7 mV. Increasing extracellular Ca 2+ (5 × 10 −3 m ) increased the amplitude of I LVA and shifted the reversal potential to +22 mV. I LVA was also blocked by extracellular Cs + (10 −4 m ) and Gd 3+ (10 −6 m ). 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’ Ca 2+ 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.