Inward Rectifier Current Research Articles

An ATP‐sensitive conductance in single smooth muscle cells from the rat vas deferens.

1. The whole-cell voltage-clamp technique was used to study the effects of extracellular ATP on smooth muscle cells isolated from the rat vas deferens. 2. ATP (1-200 microM) elicited an inward-rectifying current that was rapid in onset (less than or equal to 100 ms), reached a peak value that depended on [ATP], and desensitized in the continued presence of ATP (half-time approximately 2 s). 3. Cells recovered from desensitization when incubated in the absence of ATP (resensitization half-time approximately 2 min). 4. A comparison was made of the ability of ATP and several of its structural analogues to stimulate inward current at a negative holding potential. ATP was by far the most effective compound among the series ATP, ADP, AMP, adenosine, GTP, UTP and ITP. ADP elicited a current that was 20-25% as large as that produced by ATP, while the other compounds were ineffective at a concentration which produced a maximal ATP response. 5. AMP-CPP (alpha, beta-methylene ATP), AMP-PCP (beta, gamma-methylene ATP), and AMP-PNP (beta, gamma-imido ATP), which are relatively resistant to hydrolysis, were similarly compared to ATP. While none of these analogues elicited a current resembling the ATP-induced current, AMP-CPP and AMP-PNP each produced a small, relatively sustained inward current; AMP-PCP had little or no effect. 6. The ATP-sensitive conductance is cation selective, but does not appear to discriminate strongly between Na+, K+ and Mg2+. 7. Analysis of the fluctuations which accompany the ATP-induced current suggests that ATP controls a population of channels with a unitary current greater than 0.5 pA at -130 mV. 8. The ATP-evoked current discussed in this report may be responsible for the depolarizing effect of ATP previously described in multicellular preparations of the vas deferens.

Characterization of the inward-rectifying potassium current in cat ventricular myocytes.

Whole-cell membrane currents were measured in isolated cat ventricular myocytes using a suction-electrode voltage-clamp technique. An inward-rectifying current was identified that exhibited a time-dependent activation. The peak current appeared to have a linear voltage dependence at membrane potentials negative to the reversal potential. Inward current was sensitive to K channel blockers. In addition, varying the extracellular K+ concentration caused changes in the reversal potential and slope conductance expected for a K+ current. The voltage dependence of the chord conductance exhibited a sigmoidal relationship, increasing at more negative membrane potentials. Increasing the extracellular K+ concentration increased the maximal level of conductance and caused a shift in the relationship that was directly proportional to the change in reversal potential. Activation of the current followed a monoexponential time course, and the time constant of activation exhibited a monoexponential dependence on membrane potential. Increasing the extracellular K+ concentration caused a shift of this relationship that was directly proportional to the change in reversal potential. Inactivation of inward current became evident at more negative potentials, resulting in a negative slope region of the steady state current-voltage relationship between -140 and -180 mV. Steady state inactivation exhibited a sigmoidal voltage dependence, and recovery from inactivation followed a monoexponential time course. Removing extracellular Na+ caused a decrease in the slope of the steady state current-voltage relationship at potentials negative to -140 mV, as well as a decrease of the conductance of inward current. It was concluded that this current was IK1, the inward-rectifying K+ current found in multicellular cardiac preparations. The K+ and voltage sensitivity of IK1 activation resembled that found for the inward-rectifying K+ currents in frog skeletal muscle and various egg cell preparations. Inactivation of IK1 in isolated ventricular myocytes was viewed as being the result of two processes: the first involves a voltage-dependent change in conductance; the second involves depletion of K+ from extracellular spaces. The voltage-dependent component of inactivation was associated with the presence of extracellular Na+.

Fast inward-rectifying current accounts for anomalous rectification in olfactory cortex neurones.

The somatic membrane of guinea-pig olfactory cortex neurones in vitro (23 degrees C) was voltage clamped by means of a single-micro-electrode sample-and-hold technique. In most cells the current-voltage (I-V) relationship showed inward (anomalous) rectification with increasing hyperpolarization beyond the resting potential (ca. -80 mV). Under current-clamp conditions a time-dependent 'sag' of the hyperpolarizing electrotonic potentials was observed following an initial overshoot. No depolarizing after-potential was seen on return to the resting potential. Inward rectification was activated between -100 and -110 mV (irrespective of pre-set resting potential) and increased the membrane input conductance by up to three-fold. The rectification was unaffected by tetrodotoxin or Cd2+. Under somatic voltage clamp, hyperpolarization beyond -110 mV activated a rapid inward relaxation fitted by a single exponential. The relaxation time constant (tau on) decreased e-fold for a 40 mV hyperpolarization. (Typical values: 28 ms at -110 mV declining to 13 ms at -140 mV; external K+ concentration 3 mM, 23 degrees C). More extreme hyperpolarizations evoked a slower 'inactivation' phase (tau = 40-60 ms). A transient outward-decaying 'tail' current reflecting deactivation of inward rectification was seen on stepping from -140 mV to more positive potentials. tau off became slower with hyperpolarization. The tail current disappeared at a potential close to the expected VK but was rarely inverted to an inward-decaying tail. It is proposed that the fast inward-rectifying current of olfactory neurones (If.i.r.) is a K+ current analogous to the anomalous K+ rectifier of marine egg and frog muscle membranes. The behaviour of the inward rectifier was dependent on external K+ concentration in accordance with the unique 'V--VK' dependence of classical anomalous rectification; however, of several agents tested (external Cs+, Ba2+, Rb+, Tl+ or tetraethylammonium), only Cs+ and Ba2+ blocked If.i.r. in a time- and voltage-dependent manner. The effect of tetraethylammonium resembled that of an increase in external K+. The possible contribution of the inward rectifier to the passive cell membrane properties is discussed.