Ionic currents of outer hair cells isolated from the guinea‐pig cochlea.

Abstract

SUMMARY1. Whole-cell currents were measured in outer hair cells isolated from each turn of the organ of Corti of the guinea-pig.2. The slope input conductances at -70 mV of the cells ranged from 3-6 to 51 nS depending on the length of the cell. Shorter cells from the basal turns of the cochlea had the highest values. The membrane time constant of the cells varied from 3 to 0 2 ms from the apex to the base.3. Irrespective of the position of the cells along the cochlea, three distinct currents were found. Each type of current was found in approximately the same proportion in all cells.4. An outward K+ current was present which activated at potentials more positive than -35 mV. The current was sensitive to tetraethylammonium (30 mM), quinidine (100 AM) and nifedipine (50 /tM). It could be removed by replacing external Ca21 with Ba2+ or Mg2+. The current was also removed by substituting Nat or Cst for Kt pipette solution. This outwardly rectifying current appears similar to the calciumactivated K+ current described in other hair cells.5. The main current present at membrane potentials from -90 mV to -50 mV was a second voltage-activated K+ current. It was 50 % activated at -80 mV, and relaxed with a time constant of 20-40 ms on hyperpolarization to -120 mV. Near rest the kinetics were essentially time-independent, but depended upon the external K+ concentration. The current was blocked by 5 mm external Cs+.6. This current was highly selective for K+. Measured from reversal of the tail currents, the permeability ratio PK PNa was approximately 30: 1. Depolarization of the cell, presumed to lead to an elevation of intracellular calcium, produced a prolonged activation of the current. 7. A third current found in the cells was a cation current. By external ion replacement, the selectivity sequence was determined to be Ca2+ > Na'~K+ > choline+ > NMDG+ (respective permeabilities relative to Na: 2 9, 1P0, 0 99, 0-63 and 0 37). This current * Present address:

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

“…Thus, we measured the resting membrane potential of isolated OHCs using the whole-cell voltage-clamp technique as described by other studies [42–44]. Although hair cells are usually depolarized when the electrochemical environment bathing their apical surface is no longer present in vitro [42,45], we speculated that the Mitf -mutant OHCs would be more depolarized when compared with their WT counterpart. Resting membrane potential in our measurement was defined as the potential observed immediately upon penetrating the cell membrane with the patch electrode [42].…”

“…The resting membrane potential of hair cells is established by higher concentration of K + (inside the hair cells) and by diffusion of K + across the basolateral membrane. K + influx (leak) through the mechanotransduction channel at rest, together with the Na + /K + pump in the basolateral membrane, plays an important role in establishing and maintaining membrane potential of hair cells [42,45]. Reduction of K + influx (due to decrease of EP and/or K + concentration in the endolymph) through transduction channels leads to the reduction of K + concentration gradient across the basolateral membrane, which moves the resting membrane potential toward zero, resulting in Ca ++ influx, which further depolarizes the cells.…”

Lead (Pb2+) modulation of potassium currents of guinea pig outer hair cells

“…Channels mediating inward currents carried by potassium channels were also identified and took on the appearance of a fast partial inactivating type and a slow steady state non-inactivating type of the I K(n) type [2,13,16,17,18,23,26,27,32]. Outward going Kv were partially blocked by 25 mM TEA, 100 AM 4-AP, and by 100 AM CdCl 2 (data not shown), indicating that the currents obtained were K + currents and that parts of the current were Ca activated.…”

“…Different types of potassium conductances [delayed rectifier K channels, I K(dr) ; calcium-activated K channels, I K(Ca) ; and inward rectifier leak current, I K(n) ] of OHC of guinea pig have been reported and are purported to play a role in frequency tuning and maintaining the cell resting membrane potential [1,2,16,17,18,26,27]. K + channels have been proposed as a drug target in the treatment of myasthenia gravis, multiple sclerosis, Huntington chorea, and Alzheimer disease [40].…”

Linopirdine Blocks α9α10-Containing Nicotinic Cholinergic Receptors of Cochlear Hair Cells

“…Studies of the electrophysiological response to ACh in mammalian OHCs are hindered by the presence of a potassium current, I K,n , most likely mediated by channels containing the KCNQ4 subunit (Housley and Ashmore 1992;Marcotti and Kros 1999). I K,n provides a large potassium conductance that determines the OHCs membrane potential and membrane time constant.…”