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 Ca(2+) 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 Ni(2+) (IC(50) = 1.4 x 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 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 Gd(3+) (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' 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.
Koh
S D
SD
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA. skoh@physio.unr.edu
Monaghan
K
K
Ro
S
S
Mason
H S
HS
Kenyon
J L
JL
Sanders
K M
KM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000235:genetics; D002586:Cesium / Q000494:pharmacology; D003106:Colon / Q000166:cytology*; D005682:Gadolinium / Q000494:pharmacology; D015870:Gene Expression; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000166:cytology / Q000294:innervation / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000494:pharmacology; D013696:Temperature
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D002586:Cesium; D001464:Barium; D020748:Mibefradil; D009532:Nickel; D012964:Sodium; D005682:Gadolinium; D009529:Nicardipine; D002118:Calcium