Biomedical subjects

K Benndorf

Publications and source records attributed to K Benndorf.

At least 19 recordsLinked to original sources

PubMed2001

Role of the S2 and S3 segment in determining the activation kinetics in Kv2.1 channels.

We constructed chimeras between the rapidly activating Kv1.2 channel and the slowly activating Kv2.1 channel in order to study to what extent sequence differences within the S1-S4 region contribute to the difference in activation kinetics. The channels were expressed in Xenopus oocytes and the currents were measured with a two-microelectrode voltage-clamp technique. Substitution of the S1-S4 region of Kv2.1 subunits by the ones of Kv1.2 resulted in chimeric channels which activated more rapidly than Kv2.1. Furthermore, activation kinetics were nearly voltage-independent in contrast to the pronounced voltage-dependent activation kinetics of both parent channels. Systematic screening of the S1-S4 region by the replacement of smaller protein parts resolved that the main functional changes generated by the S1-S4 substitution were generated by the S2 and the S3 segment. However, the effects of these segments were different: The S3 substitution reduced the effective gating charge and accelerated both a voltage-dependent and a voltage-independent component of the activation time course. In contrast, the S2 substitution accelerated predominantly the voltage-dependent component of the activation time course thereby leaving the effective gating charge unchanged. It is concluded that the S2 and the S3 segment determine the activation kinetics in a specific manner.

Amino Acid Sequence↗

PubMed2001

Serum deprivation and NGF induce and modulate voltage-gated Na(+) currents in human astrocytoma cell lines.

Glial tumor cells derived from primary tissue express large voltage-gated Na(+) currents, whereas glioma cell lines usually lack this feature. We studied the effect of serum deprivation on the expression of Na(+) currents in two astrocytoma cell lines (1321N1 and A172). Serum deprivation for more than 2 days sufficed to induce large Na(+) currents in both cell lines; 300 nM of the specific blocker of voltage-gated Na(+) channels, tetrodotoxin, blocked these currents by about 85%. During serum deprivation, the cells also underwent morphological changes that were characterized by cell rounding and outgrowth of processes. Treatment with 100 ng/ml nerve growth factor (NGF) promoted these morphological changes and also accelerated the development of Na(+) currents. In 1321N1 cells, NGF increased the Na(+) current density after short serum deprivation (3--6 d) and changed several gating properties after longer serum deprivation (9--13 d). In comparison with cells from the early culture stage (3--6 d), the steady-state inactivation of the Na(+) current was shifted by -24 mV in NGF-treated cells from the late (9--13 d) culture stage. In untreated cells, this shift was only -13 mV. NGF accelerated the kinetics of inactivation and shifted the current-voltage relationship in cells from the late culture stage by -14 mV. In A172 cells, most of these effects were present already after short serum deprivation either in presence or absence of NGF. It is concluded that in astrocytoma cells, Na(+) currents are induced by serum deprivation and are modulated by NGF. This result supports the idea that NFG controls Na(+) currents in these cells by autocrine stimulation.

Astrocytoma↗

PubMed2001

Dibenzylamine--a novel blocker of the voltage-dependent K+ current in myocardial mouse cells.

Ventricular myocytes of the mouse ventricle were voltage clamped with a patch-clamp technique in the whole-cell configuration. At depolarizing voltage pulses, these myocytes develop a large voltage-dependent K+ outward current. Application of the drug dibenzylamine (DBA) to the bath solution blocked the voltage-dependent K+ current. The concentration/response relationship for the peak current at +40 mV indicates a 1:1 binding of the drug to the receptor with a concentration of half maximum effect of 43.1 micromol/l. The block did not require activation of the channels by depolarizing pulses. At concentrations causing partial block (25 micromol/l), the block was independent of voltage. At the same concentration, DBA completely blocked the slow component of the recovery from inactivation (-80 mV) whereas steady-state inactivation was not altered. It is concluded that DBA is a novel blocker of the voltage-dependent K+ current in mouse cardiac myocytes which preferentially affects the current component generating the slow recovery from inactivation.

Animals↗

PubMed2001

Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome.

Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+) channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3). Excessive prolongation of the action potential at low heart rates predisposes individuals with LQT3 to fatal arrhythmias, typically at rest or during sleep. Here we report that mice heterozygous for a knock-in KPQ-deletion (SCN5A(Delta/+)) show the essential LQT3 features and spontaneously develop life-threatening polymorphous ventricular arrhythmias. Unexpectedly, sudden accelerations in heart rate or premature beats caused lengthening of the action potential with early afterdepolarization and triggered arrhythmias in Scn5a(Delta/+) mice. Adrenergic agonists normalized the response to rate acceleration in vitro and suppressed arrhythmias upon premature stimulation in vivo. These results show the possible risk of sudden heart-rate accelerations. The Scn5a(Delta/+) mouse with its predisposition for pacing-induced arrhythmia might be useful for the development of new treatments for the LQT3 syndrome.

Adrenergic beta-Agonists↗

PubMed2001

Molecular regions controlling the activity of CNG channels.

The alpha subunits of CNG channels of retinal photoreceptors (rod) and olfactory neurons (olf) are proteins that consist of a cytoplasmic NH(2) terminus, a transmembrane core region (including the segments S1-S6), and a cytoplasmic COOH terminus. The COOH terminus contains a cyclic nucleotide monophosphate binding domain NBD) that is linked by the C-linker (CL) to the core region. The binding of cyclic nucleotides to the NBD promotes channel opening by an allosteric mechanism. We examined why the sensitivity to cGMP is 22 times higher in olf than in rod by constructing chimeric channels and determining the [cGMP] causing half maximum channel activity (EC(50)). The characteristic difference in the EC(50) value between rod and olf was introduced by the NH(2) terminus and the core-CL region, whereas the NBD showed a paradoxical effect. The difference of the free energy difference Delta(DeltaG) was determined for each of these three regions with all possible combinations of the other two regions. For rod regions with respect to corresponding olf regions, the open channel conformation was destabilized by the NH(2) terminus (Delta(DeltaG) = -1.0 to -2.0 RT) and the core-CL region (Delta(DeltaG) = -2.0 to -2.9 RT), whereas it was stabilized by the NBD (Delta(DeltaG) = 0.3 to 1.1 RT). The NH(2) terminus deletion mutants of rod and olf differed by Delta(DeltaG) of only 0.9 RT, whereas the wild-type channels differed by the much larger value of 3.1 RT. The results show that in rod and olf, the NH(2) terminus, the core-CL region, and the NBD differ by characteristic Delta(DeltaG) values that do not depend on the specific composition of the other two regions and that the NH(2) terminus generates the main portion of Delta(DeltaG) between the wild-type channels.

Animals↗

PubMed2000

Large conductance Ca(2+)-activated K(+) channels in human meningioma cells.

Cells from ten human meningiomas were electrophysiologically characterized in both living tissue slices and primary cultures. In whole cells, depolarization to voltages higher than +80 mV evoked a large K(+) outward current, which could be blocked by iberiotoxin (100 nm) and TEA (half blocking concentration IC(50) = 5.3 mm). Raising the internal Ca(2+) from 10 nm to 2 mm shifted the voltage of half-maximum activation (V(1/2)) of the K(+) current from +106 to +4 mV. Respective inside-out patch recordings showed a voltage- and Ca(2+)-activated (BK(Ca)) K(+) channel with a conductance of 296 pS (130 mm K(+) at both sides of the patch). V(1/2) of single-channel currents was +6, -12, -46, and -68 mV in the presence of 1, 10, 100, and 1000 microm Ca(2+), respectively, at the internal face of the patch. In cell-attached patches the open probability (P(o)) of BK(Ca) channels was nearly zero at potentials below +80 mV, matching the activation threshold for whole-cell K(+) currents with 10 nm Ca(2+) in the pipette. Application of 20 microm cytochalasin D increased P(o) of BK(Ca) channels in cell-attached patches within minutes. These data suggest that the activation of BK(Ca) channels in meningioma cells does not only depend on voltage and internal Ca(2+) but is also controlled by the cytoskeleton.

Aged↗

PubMed2000

Structural elements determining activation kinetics in Kv2.1.

Voltage-dependent K+ channels open when depolarizing the membrane voltage. Among the different alpha-subunits, the time course of current activation spreads over a wide range. The structural basis underlying this diversity is not known. We constructed multiple chimeras between two voltage-dependent K+ channels, the rapidly activating Kv1.2 and the slowly activating Kv2.1, and we focused on the C-terminal half of the core region. The general strategy was to substitute parts of Kv2.1 by corresponding parts of Kv1.2 and to test for an acceleration of activation. We identified three regions which contribute to the determination of the activation kinetics: the S5-pore linker, the deep pore, and the S4-segment.

Amino Acid Sequence↗

PubMed1999

Inward rectification in KATP channels: a pH switch in the pore.

Inward-rectifier potassium channels (Kir channels) stabilize the resting membrane potential and set a threshold for excitation in many types of cell. This function arises from voltage-dependent rectification of these channels due to blockage by intracellular polyamines. In all Kir channels studied to date, the voltage-dependence of rectification is either strong or weak. Here we show that in cardiac as well as in cloned KATP channels (Kir6.2 + sulfonylurea receptor) polyamine-mediated rectification is not fixed but changes with intracellular pH in the physiological range: inward-rectification is prominent at basic pH, while at acidic pH rectification is very weak. The pH-dependence of polyamine block is specific for KATP as shown in experiments with other Kir channels. Systematic mutagenesis revealed a titratable C-terminal histidine residue (H216) in Kir6.2 to be the structural determinant, and electrostatic interaction between this residue and polyamines was shown to be the molecular mechanism underlying pH-dependent rectification. This pH-dependent block of KATP channels may represent a novel and direct link between excitation and intracellular pH.

ATP-Binding Cassette Transporters↗

PubMed1999

Anoxia generates rapid and massive opening of KATP channels in ventricular cardiac myocytes.

OBJECTIVE: The aim was to improve the measurement of both the time course and amplitude of anoxia-induced KATP-channel current (IKATP) in isolated heart cells to specify the role of these channels in the time course of K+ accumulation in the ischemic myocardium. METHODS: Ionic currents in isolated ventricular heart cells of the mouse were measured with a patch clamp technique under normoxic conditions (atmospheric pO2), during wash-out of oxygen, and under anoxic conditions (pO2 < 0.2 mmHg). During the measurement, the actual pO2 in the close proximity of the cell was determined with an optical technique by exciting Pd-meso-tetra(4-carboxyphenyl)porphin with light flashes of 508-570 nm and evaluating the quenching kinetics of the emitted phosphorescence signal at 630-700 nm. These quenching kinetics steeply depend on pO2 and can be evaluated best at pO2 values near 0 mmHg. RESULTS: Out of 28 cells, 23 cells started to develop IKATP at pO2 values between 0 and 0.4 mmHg, i.e. in the range of the level of half maximum activity of the cytochrome oxidase. The remaining five cells developed IKATP between 0.4 and 1.8 mmHg. With respect to the time course, 18 out of 27 cells started to develop IKATP within the first minute after pO2 had decreased to values below 0.2 mmHg. The amplitude of IKATP induced by anoxia and various metabolic inhibitors was large, 29 +/- 12 and 48 +/- 21 nA (+40 mV), respectively. The anoxia-induced IKATP was significantly smaller than IKATP induced by metabolic inhibitors. During the pulses of 50 ms duration to +40 mV, the amplitude of IKATP decayed and, after clamping back to -80 mV, IKATP generated large tail currents. This suggests a notable change in the concentration gradient of K+ ions in the time range of tens of milliseconds. CONCLUSIONS: The results in isolated myocytes indicate that KATP channels open sufficiently rapidly after starting anoxia and generate sufficiently large conductance at maintained anoxia to explain both the time course and magnitude of the ischemic K+ accumulation if an appropriate counter-ion flux is available.

Animals↗

PubMed1999

Gating by cyclic GMP and voltage in the alpha subunit of the cyclic GMP-gated channel from rod photoreceptors.

Gating by cGMP and voltage of the alpha subunit of the cGMP-gated channel from rod photoreceptor was examined with a patch-clamp technique. The channels were expressed in Xenopus oocytes. At low [cGMP] (<20 microM), the current displayed strong outward rectification. At low and high (700 microM) [cGMP], the channel activity was dominated by only one conductance level. Therefore, the outward rectification at low [cGMP] results solely from an increase in the open probability, P(o). Kinetic analysis of single-channel openings revealed two exponential distributions. At low [cGMP], the larger P(o) at positive voltages with respect to negative voltages is caused by an increased frequency of openings in both components of the open-time distribution. In macroscopic currents, depolarizing voltage steps, starting from -100 mV, generated a time-dependent current that increased with the step size (activation). At low [cGMP] (20 microM), the degree of activation was large and the time course was slow, whereas at saturating [cGMP] (7 mM) the respective changes were small and fast. The dose-response relation at -100 mV was shifted to the right and saturated at significantly lower P(o) values with respect to that at +100 mV (0.77 vs. 0.96). P(o) was determined as function of the [cGMP] (at +100 and -100 mV) and voltage (at 20, 70, and 700 microM, and 7 mM cGMP). Both relations could be fitted with an allosteric state model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric opening reaction. At saturating [cGMP] (7 mM), the activation time course was monoexponential, which allowed us to determine the individual rate constants for the allosteric reaction. For the rapid rate constants of cGMP binding and unbinding, lower limits are determined. It is concluded that an allosteric model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric reaction, describes the cGMP- and voltage-dependent gating of cGMP-gated channels adequately.

Animals↗

PubMed1998

Inactivation of single cardiac Na+ channels in three different gating modes.

In small cell-attached patches containing one and only one Na+ channel, inactivation was studied in three different gating modes, namely, the fast-inactivating F mode and the more slowly inactivating S mode and P mode with similar inactivation kinetics. In each of these modes, ensemble-averaged currents could be fitted with a Hodgkin-Huxley-type model with a single exponential for inactivation (tauh). tauh declined from 1.0 ms at -60 mV to 0.1 ms at 0 mV in the F mode, from 4.6 ms at -40 mV to 1.1 ms at 0 mV in the S mode, and from 4.5 ms at -40 mV to 0.8 ms at +20 mV in the P mode, respectively. The probability of non-empty traces (net), the mean number of openings per non-empty trace (op/tr), and the mean open probability per trace (popen) were evaluated at 4-ms test pulses. net inclined from 30% at -60 mV to 63% at 0 mV in the F mode, from 4% at -90 mV to 90% at 0 mV in the S mode, and from 2% at -60 mV to 79% at +20 mV in the P mode. op/tr declined from 1.4 at -60 mV to 1.1 at 0 mV in the F mode, from 4.0 at -60 mV to 1.2 at 0 mV in the S mode, and from 2.9 at -40 mV to 1.6 at +20 mV in the P mode. popen was bell-shaped with a maximum of 5% at -30 mV in the F mode, 48% at -50 mV in the S mode, and 16% at 0 mV in the P mode. It is concluded that 1) a switch between F and S modes may reflect a functional change of inactivation, 2) a switch between S and P modes may reflect a functional change of activation, 3) tauh is mainly determined by the latency until the first channel opening in the F mode and by the number of reopenings in the S and P modes, 4) at least in the S and P modes, inactivation is independent of pore opening, and 5) in the S mode, mainly open channels inactivate, and in the P mode, mainly closed channels inactivate.

Animals↗

PubMed1997

3-hydroxybutyrate blocks the transient K+ outward current in myocardial mouse cells in a stereoselective fashion.

1. Mouse ventricular myocytes develop a large transient K+ outward current (I(TO)) which accelerates repolarization and is a crucial determinant for the regulation of the action potential duration at various heart rates. The effect of 3-hydroxybutyrate on I(TO) was investigated under voltage- and current-clamp conditions. 2. The drug blocked I(TO) in a stereoselective manner with the L-enantiomer being the effective and the D-enantiomer, the ineffective form. The blocking action of the L-enantiomer was established immediately and it could be completely washed out within several tens of seconds. 3. The dose-response characteristic for the peak I(TO) showed a strict 1:1 binding of the drug to the receptor with a concentration of half-maximum effect of 2.1 mmol l(-1). 4. The action of L-hydroxybutyrate was voltage independent, did not need channel opening and preferentially affected the slow component of both inactivation and recovery from inactivation. 5. At the high concentration of 20 mmol l(-1) the optically inactive form, the racemate, did not affect I(TO), indicating that the ineffective D-enantiomer interacts with the channels at much lower concentrations. 6. At a concentration of 10 mmol l(-1), L-hydroxybutyrate prolonged the action potential by 218 +/- 26 and 127 +/- 10% (means +/- S.E.M.) at 50 and 90% repolarization, respectively. 7. It is concluded that the non-physiological L-hydroxybutyrate is a novel type of blocker of I(TO), It interacts either with the channel itself, or with a receptor protein closely related to the channel and preferentially affects slow inactivation.

3-Hydroxybutyric Acid↗

PubMed1997

Functional differences of a Kv2.1 channel and a Kv2.1/Kv1.2S4-chimera are confined to a concerted voltage shift of various gating parameters.

When expressed in Xenopus oocytes, the voltage-dependent K+ channels Kv1.2 and Kv2.1 have similar steady state parameters of activation but the kinetics of activation is significantly faster in the Kv1.2 channels. Activation results from intramolecular arrangements which start with the movement of the voltage sensor and end with the opening of the pore. The S4-segment and the H5-loop comprise at least part of the respective involved structural elements. The molecular mechanism of coupling between sensing of voltage and opening of the pore is less well understood. We have measured whole cell and single channel ionic currents in the rapidly activating Kv1.2 channel of the rat, the slowly activating Kv2.1 channel of the human, and in an S4-chimera Kv2.1/Kv1.2S4. With respect to the Kv2.1 channel, steady state activation and steady state C-type inactivation of the chimeric channel are shifted by more than 50 mV in the depolarizing direction. The property of rapid activation in Kv1.2 channels was not transferred to the Kv2.1 channels with the transplanted S4-region. Instead, the kinetics of activation, deactivation, and recovery from C-type inactivation as well as the voltage sensitivity of the 4-aminopyridine block are similar to the corresponding processes in Kv2.1 channels if they are related to the steady state activation and inactivation, respectively. The unitary current and the mean open time of single channel openings of the S4-chimeric channels resemble the respective values of Kv2.1 channels. It is concluded that the insertion of the S4-segment of Kv1.2 channels into Kv2.1 channels modifies the gating at the early steps of activation leaving all properties associated with the open state(s) of the Kv2.1 channels unaffected.

4-Aminopyridine↗

PubMed1996

Functional interaction between K(ATP) channels and the Na(+)-K(+) pump in metabolically inhibited heart cells of the guinea-pig.

1. Transmembrane current through ATP-regulated K(+) channels (IK(ATP)) was measured in ventricular heart cells of the guinea-pig in the whole-cell and cell-attached patch configurations under conditions of metabolic poisoning with the mitochondrial uncoupler 2,4-dinitrophenol (DNP). 2. Maintained exposure of the cells to DNP resulted in a transient appearance of whole-cell IK(ATP) When IK(ATP) had reached several nanoamps, blocking the forward-running Na(+)-K(+) pump with 0.5 mM strophanthidin decreased IK(ATP) after a delay. The time course of this decrease could be described by a single exponential function, which yielded a time constant(T)of 4.51+/- 1.89 s (n=8). 3. Hyperpolarization from 0 mV to -100 or -150 mV for 2 s caused IK(ATP) (measured at 0 mV) to decrease by 34.2 +/- 14.1 % (n = 8) and 37.6 +/- 9.4% (n = 8), respectively. After the hyperpolarizing pulse, IK(ATP) returned to its higher initial level within a couple of seconds. 4. Driving the pump backwards by removing the extracellular K(+) ions caused the permanent disappearance of DNP-induced IK(ATP). 5. Application of 0.5 mM strophanthidin in the absence of external K(+) ions induced a transient increase in IK(ATP), as did washing out the glycoside (n = 5). 6. When pump action was inhibited by using Na(+), K(+)-free Tyrode solution (see Methods) in the bath, strophanthidin did not have a comparable direct effect on IK(ATP). 7. In cell-attached patches, strophanthidin applied via the bath caused a reduction in IK(ATP) with a similar time course to that in whole-cell experiments. This suggests that the interaction between the pump molecules and the K(ATP) channels is not restricted to closely neighbouring molecules. 8. The data support the hypothesis that [ATP] at the cytosolic face of the membrane may drop to practically zero, thereby passing an 'ATP window' in which the channels first open and then close, and that the submembrane [ATP] is readily controlled by the cytosolic [ATP].

2,4-Dinitrophenol↗

PubMed1995

Secretoneurin-immunoreactivity in nerve terminals apposing identified preganglionic sympathetic neurons in the rat: colocalization with substance P and enkephalin.

Preganglionic sympathetic neurons projecting to the superior cervical ganglion are innervated by nerve fibers containing classical neurotransmitters as well as neuropeptides. In this study we examined the possible participation of a novel peptide, secretoneurin (a cleavage product of secretogranin II), in regulation of sympathetic outflow to head and neck by using a retrograde labelling-technique combined with immunohistochemistry. In addition, the coexistence of secretoneurin with substance P and leu-enkephalin, peptides known to innervate preganglionic neurons, was investigated. The majority of retrogradely labeled neurons were localized in the nucleus intermediolateralis of spinal cord segments T1-T3 (maximum at T2). Nearly all of Fast Blue positive neuronal perikarya were apposed by nerve fibers and terminals exhibiting immunoreactivity to secretoneurin. The main secretoneurin-immunoreactive form found in the upper thoracic segments corresponded to the free peptide secretoneurin as revealed by chromatography and radioimmunoassay. More than half of labeled neurons were surrounded by nerve endings containing in addition substance P or leu-enkephalin which were also, however, less frequently colocalized. Our results suggest that secretoneurin influences the activity of preganglionic sympathetic neurons projecting to the superior cervical ganglion. Regarding their frequent colocalization with substance P and leu-enkephalin, functional interactions of these peptides on preganglionic sympathetic nerve activity have to be considered.

Animals↗

PubMed1995

Voltage-dependent properties of three different gating modes in single cardiac Na+ channels.

Three different modes of Na+ channel action, the F mode (fast inactivating), the S mode (slowly inactivating), and the P mode (persistent), were studied at different potentials in exceptionally small cell-attached patches containing one and only one channel. Switching between the modes was independent of voltage. In the F mode, the mean open time (tau o) at -30 and -40 mV was 0.14 and 0.16 ms, respectively, which was significantly larger than at -60 and 0 mV, where the values were 0.07 and 0.08 ms, respectively. The time before which half of the first channel openings occurred (t 0.5), decreased from 0.58 ms at -60 mV to 0.14 ms at 0 mV. The fit of steady-state activation with a Boltzmann function yielded a half-maximum value (V 0.5) at -48.1 mV and a slope (k) of 5.6 mV. The mean open time in the S mode increased steadily from 0.12 ms at -80 mV to 1.09 ms at -30 mV, but was not prolonged further at -20 mV (1.07 ms). Concomitantly, t 0.5 decreased from 1.61 ms at -80 mV to 0.22 ms at -20mV. Here the midpoint of steady-state activation was found at -61.2 mV, and the slope was 8.7 mV. The mean open time in the P mode increased from 0.07 ms at -60 mV to 0.45 ms at 0 mV and t 0.5 declined from 2.14 ms at -60 mV to 0.19 ms at +20 mV. Steady-state activation had its midpoint at -14.7 mV, and the slope was 10.9 mV. It is concluded that a single Na+ channel may switch among the F, S, and P mode and that the three modes differ by a characteristic pattern of voltage dependence of tau 0, t 0.5, and steady-state activation.

Animals↗

PubMed1995

Multimodal action of single Na+ channels in myocardial mouse cells.

Unitary Na+ currents of myocardial mouse cells were studied at room temperature in 10 cell-attached patches, each containing one and only one channel. Small-pore patch pipettes (resistance 10-97 M omega when filled with 200% Tyrode's solution) with exceptionally thick walls were used. Observed were both rapidly inactivating (6 patches) and slowly inactivating (3 patches) Na+ currents. In one patch, a slow transition from rather fast to slow inactivation was detected over a time of 0.5 h. A short and a long component of the open-channel life time were recorded at the beginning, but only a short one at the end of the experiment. Concomitantly, the first latency was slowed. Amplitude histograms showed that the electrochemical driving force across the pore of the channel did not change during this time. In three patches, a fast and repetitive switching between different modes of Na+ channel action could be clearly identified by plotting the long-time course of the averaged current per trace. The ensemble-averaged current formed in each mode was different in kinetics and amplitude. Each mode had a characteristic mean open-channel life time and distribution of first latency, but the predominant single-channel current amplitude was unaffected by mode switches. It is concluded that two types of changes in kinetics may happen in a single Na+ channel: fast and reversible switches between different modes, and a slow loss of inactivation.

Animals↗

PubMed1994

ATP-sensitive K+ channels in heart muscle cells first open and subsequently close at maintained anoxia.

In ventricular myocardial cells of the guinea pig and the mouse, anoxia caused after a mean latency of 439 +/- 141 s and 129 +/- 23 s (mean +/- S.E.M.), respectively, a large current through KATP-channels. This current disappeared within several seconds when reoxygenating the cells but decayed also completely at maintained anoxia. The kinetics of the latter process, however, were much slower and obeyed an approximately monoexponential time course with time constants in the range of 30 s. The results suggest that in the ischaemic myocardium KATP-channels contribute only to the initial phase of extracellular K+ accumulation.

Adenosine Triphosphate↗