Inward current

Antiarrhythmic Drugs. Figure 1 Transmembrane ionic currents of the cardiac action potential. In the middle of the figure, a typical cardiac action potential is shown as can be obtained from the ventricular myocardium (upper trace). Below, the contribution of the various transmembrane currents is indicated. Currents below the zeroline are inward currents above the zero line are outward fluxes. In the left column the name of the current is given and in the right column the possible clone redrawn and modified after [5]. 

Voltage-dependent Ca2+ channels that are activated at a membrane potential around -30 mV with a maximal inward current around OmV. 

Inward Rectifier K+ Channels. Figure 2 High [K+] inside cells relative to outside results in normal rectification, whereby outward (positive by convention) potassium currents (/) when cells are depolarized (is positive relative to EK), are biggerthan inward (negative) currents at hyperpolarized (negative) voltages. Inward or anomalous rectifiers show strong or weak inward rectification whereby outward currents are smaller than inward currents. 

TK NKxr displays a broad distribution in both peripheral tissues and in the central nervous system (CNS). In both CNS and enteric neurons, NKxr stimulation increase their excitability, whereas in trigeminal ganglion neurons SP has no intrinsic electrophysio-logical effects but is capable to enhance the amplitude of the inward current induced by the stimulation of serotonin 5-HT3 recqrtors. This enhancement dqjends on the activation of PKC via the stimulation of NKX recqrtors. This is an interesting case of receptor cross talk. Other functions of NKxr have been also highlighted. 

In cerebellar Purkinje cells, a TTX-sensitive inward current is elicited, when the membrane was partially repolarized after strong depolarization. This resurgent current contributes to high-frequency repetitive firing of Purkinje neurons. The resurgent current results from open channel block by the cytoplasmic tail of the (34 subunit. The med Nav 1.6 mutant mice show defective synaptic transmission in the neuromuscular junction and degeneration of cerebellar Purkinje cells. 

Figure 3. (+)-Anatoxin-a (AnTx) and ACh induced single ion channel currents in isolated frog muscle fibers. Open channels with 32 pS conductance are downward deflections (inward current at hyperpolarized potentials). The currents shown on the left are all at one potential. The duration of channel open events had a similar voltage-dependence for both ACh and (+)-anatoxin-a. With ACh, the events were most often singular, while with (+)-anatoxin-a the events were shorter and were more frequently paired so that the mean duration of the exponentially distributed open times and selected membrane holding potentials was approximately one-half, independent of the concentration of the agonist applied.

The electrophysiological experiments reported here and done with patch-clamp techniques support this idea. The external application of MTX to isolated cardiac myocytes caused a sustained inward current which was carried by Ca . MTX did not increase the voltage-dependent Ca channel current, and both the time dependence and voltage dependence of the MTX-induced current were clearly different from those of the usual Ca channel current. These results suggest that the MTX-induced steady current is different from the usual voltage-dependent Ca channel current, and that this is possibly a current which flows through a new type of Ca -permeable channel. Tbe steady current described here may be responsible for the highly enhanced Ca influx induced by MTX and could account for the excitatory action of MTX on smooth and cardiac muscles. 

Piller SC, Jans P, Gage PW, Jans DA (1998) Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons implications for AIDS pathology. Proc Natl Acad Sci USA 95 4595-4600... 

Cl -channels are also present in neuroendocrine cells such as the AtT-20 pituitary cell line [30]. Ca -dependent and voltage-activated slow Cl -currents were found. These Cl -currents could subserve a role comparable to that of Cl -currents in renin-secreting cells or mast cells [13,14]. Along these lines, it has been speculated that the slow Cl inward currents may influence the firing rate of these neuroendocrine cells [30]. 

In experiments using oxidant stress induced by the photoactivation of rose bengal (10 nM), a 75% decline in the calcium inward current was observed after 10 min, with only a sUght acceleration in the inactivation kinetics of the current (Shattock etal., 1990). However, this decline in the calcium inward current appears to occur secondary to an oxidant stress-induced calcium overload and not as... 

The studies of Bhatnager et al. (1990) and Beresewicz and Horackova (1991) also report a significant and important increase in the inward movement of Na through the TTX-sensitive Na channel in cells exposed to oxidant stress. It is likely that this increased inward current may play a role in prolonging the action potential and in loading the cell with sodium. Both of these effects would combine to create a situation that would tend to load the cell with calcium through alteration in the activity of the Na/Ca exchange mechanism (Matsuura et al., 1991). 

Benndorf, K., Friedrich, M. and Hirche, H. (1991). Reoxygenation-induced arrhythmogenic transient inward currents in isolated cells of the guinea-pig heart. Pflugers Arch. 418, 248-260. 

Fedida, D., Noble, D., Rankin, A.C. and Spindler, A.J. (1987). The arrhythmogenic transient inward current iTI and related contraction in isolated guinea-pig ventricular myocytes. J. Physiol. 392, 523-542. 

Karagueuzian, H.S. and Katzung, B.G. (1982). Voltage-clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle. J. Physiol, 327, 255-271. 

Kass, R.S., Tsien, R.W. and Weingart, R. (1978). Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J. Physiol. 281, 209-226. 

Matsuura, H. and Shattock, M.J. (1991a). Membrane potential fluctuations and transient inward currents induced by reactive oxygen intermediates in isolated rabbit ventricular cells. Circ. Res. 68, 319-329. 

Inamura K. and Kashiwayanagi M. (2000b). Inward current responses to urinary substances in rat vomeronasal sensory neurons. Eur J Neurosci 12, 3529-3536. 

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