Radhakrishnan Gnanasambandam
University at Buffalo
Analytical chemistryConductanceBiophysicsMutantPatch clampKineticsMembrane potentialChemistryGatingLysineArginineMechanosensitive ion channelPeptidePIEZO1Lipid bilayerMechanosensitive channelsMembraneMutationIon channelBiochemistryStereochemistryDivalentBiologyCell biology
Publications 23
#2Chilman BaeH-Index: 12
Last. Philip A. GottliebH-Index: 32
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: PIEZO1 and PIEZO2 are mechanosensitive channels (MSCs) important for cellular function and mutations in them lead to human disorders. We examined how functional heteromers form between subunits of PIEZO1 using the mutants E2117K, E2117D, and E2117A. Homomers of E2117K do not conduct. E2117A homomers have low conductance with rapid inactivation, and those of E2117D have high conductance with slow inactivation. Pairing E2117K with E2117D or E2117A with E2117D gave rise to new channel species rep...
2 CitationsSource
#1Radhakrishnan Gnanasambandam (UB: University at Buffalo)H-Index: 10
#2Alicia Rivera (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 30
Last. Seth L. AlperH-Index: 84
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6 CitationsSource
#1Radhakrishnan Gnanasambandam (SUNY: State University of New York System)H-Index: 10
#2Morten Schak Nielsen (National Research Foundation of South Africa)H-Index: 20
Last. Jakob Kisbye Dreyer (UCPH: University of Copenhagen)H-Index: 12
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Researchers can investigate the mechanistic and molecular basis of many physiological phenomena in cells by analyzing the fundamental properties of single ion channels. These analyses entail recording single channel currents and measuring current amplitudes and transition rates between conductance states. Since most electrophysiological recordings contain noise, the data analysis can proceed by idealizing the recordings to isolate the true currents from the noise. This de-noising can be accompli...
15 CitationsSource
#1Philip A. Gottlieb (UB: University at Buffalo)H-Index: 32
#2Mohammad Mehdi Maneshi (UB: University at Buffalo)H-Index: 6
Last. Frederick Sachs (UB: University at Buffalo)H-Index: 77
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PIEZO1 is a eukaryotic mechanosensitive ion channel that is cation selective and rapidly inactivates. Using fluid shear stress as a stimulus generated in a microfluidic chamber, we have monitored PIEZO activity in the presence of various peptides. To do so, we first developed a cell line that overexpresses the PIEZO1 channel in HEK293T cells. We estimate that there are about 5000 channels per cell. These cells are seeded in the microfluidic chamber and loaded with calcium indicator. A pressure s...
#1Radhakrishnan Gnanasambandam (SUNY: State University of New York System)H-Index: 10
#2Chiranjib Ghatak (KU: University of Kansas)H-Index: 22
Last. Thomas M. Suchyna (SUNY: State University of New York System)H-Index: 24
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Abstract GsMTx4 is a spider venom peptide that inhibits cationic mechanosensitive channels (MSCs). It has six lysine residues that have been proposed to affect membrane binding. We synthesized six analogs with single lysine-to-glutamate substitutions and tested them against Piezo1 channels in outside-out patches and independently measured lipid binding. Four analogs had ∼20% lower efficacy than the wild-type (WT) peptide. The equilibrium constants calculated from the rates of inhibition and wash...
65 CitationsSource
#1Mohammad Mehdi Maneshi (UB: University at Buffalo)H-Index: 6
#2Bruce A. Maki (UB: University at Buffalo)H-Index: 6
Last. Susan Z. Hua (UB: University at Buffalo)H-Index: 24
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While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifen...
39 CitationsSource
#1Radhakrishnan Gnanasambandam (UB: University at Buffalo)H-Index: 10
#2Philip A. Gottlieb (UB: University at Buffalo)H-Index: 32
Last. Fredrick Sachs (UB: University at Buffalo)H-Index: 4
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Abstract Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300 kD monomer has an N-terminal propeller blade-like mechanosensing module, which can conf...
10 CitationsSource
#1Anthony W. Peng (University of Colorado Denver)H-Index: 13
#2Radhakrishnan Gnanasambandam (SUNY: State University of New York System)H-Index: 10
Last. Anthony J. Ricci (Stanford University)H-Index: 36
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The auditory system is able to detect movement down to atomic dimensions. This sensitivity comes in part from mechanisms associated with gating of hair cell mechanoelectric transduction (MET) channels. MET channels, located at the tops of stereocilia, are poised to detect tension induced by hair bundle deflection. Hair bundle deflection generates a force by pulling on tip-link proteins connecting adjacent stereocilia. The resting open probability ( P open ) of MET channels determines the lineari...
46 CitationsSource