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

1. 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 x 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. 2. 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. 3. I-LVA was inhibited by Ni2+ (IC50 = 1.4 x 10(-5) M), mibefradil (10(-6) to 10(-5) M), and extracellular Ba2+. Replacement of extracellular Na+ with N-methyl-D-glucamine inhibited I-LVA and shifted the reversal potential to -7 mV. Increasing extracellular Ca2+ (5 x 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 Gd3+ (10(-6) M). 4. Warming increased the rates of activation and deactivation without affecting the amplitude of the peak current. 5. 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.